СПОСОБЫ ЛЕЧЕНИЯ ЭПИЛЕПСИИ ИЛИ ЭПИЛЕПТИЧЕСКОГО СТАТУСА

Изобретение относится к области медицины, а именно к фармакологии, и предназначено для приготовления состава, содержащего аллопрегнанолон. Способ приготовления состава, содержащего аллопрегнанолон, включает предоставление стадии смешивания с большим сдвиговым усилием водной композиции, содержащей 5 мг/мл аллопрегнанолона и 25% сульфобутилового эфира β-циклодекстрина. Использование изобретения позволяет приготовить состав аллопрегнанолона, который может быть использован для лечения эпилепсии или эпилептического статуса. 2 з.п. ф-лы, 2 ил., 1 табл., 2 пр.

ИНДИВИДУАЛЬНЫЕ ФОРМЫ ЭНАНТИОМЕРОВ, А ТАКЖЕ ИХ СМЕСИ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ ПРОТИВОСУДОРОЖНЫМ ДЕЙСТВИЕМ

Описываются новые индивидуальные формы энантиомеров, а также их смеси, отличающиеся тем, что преобладает один энантиомер карбаматов 2-фенил-1,2-энантиолов, представленных структурной формулой (I), где фенильное кольцо содержит в качестве заместителей 1 - 5 атомов галогена, выбранного из фтора, хлора, брома или йода, и R1 и R2 - водород. Указанные новые соединения эффективны при лечении расстройств центральной нервной системы, особенно в качестве антиконвульсивных средств. Описывается также фармацевтическая композиция, обладающая противосудорожным действием. 6 с. и 14 з.п.ф-лы, 2 табл.

СПОСОБЫ ЛЕЧЕНИЯ ЭПИЛЕПСИИ ИЛИ ЭПИЛЕПТИЧЕСКОГО СТАТУСА

Изобретение относится к медицине, а именно неврологии, и может быть использовано для лечения индивида, имеющего супер-рефрактерный эпилептический статус (SRSE). Для этого указанному индивиду вводят эффективное количество аллопрегнанолона, при этом одновременно с указанным введением индивид находится под действием общего наркоза. Изобретение обеспечивает лечение пациента с SRSE. 34 з.п. ф-лы, 2 ил., 1 табл., 2 пр.

АРИЛКОНДЕНСИРОВАННЫЕ АЗАПОЛИЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ

... 1. Соединения формулы (I) где R1 представляет собой -COOR4, где R4 представляет собой группу формулы R2 и R3, вместе с бензольным кольцом, к которому они присоединены, образуют бициклическую кольцевую систему, выбранную из следующих: где один из атомов углерода кольца А необязательно может быть замещен кислородом или N(C1-C6)алкилом; где R11 и R12 выбирают, независимо, из водорода, (C1-C6)алкила; и (C1-C6)алкокси(C0-C6)алкила-, в котором общее число атомов углерода не превышает шесть, и где любая из алкильных групп необязательно может быть замещена одним-семью атомами фтора; нитро, циано, галогена, амино, (C1-C6 )алкиламино-, ((C1-C6 )алкил)2амино-, -СО2R5, -CONR6R7, -SO2NR8R9, -C(=O)R10, -XC(=O)R10, фенила, моноциклического гетероарила, или, когда они связаны с атомом азота, группы формулы каждый R5, R6, R7, R8, R9 и R10 выбирают, независимо, из водорода и (C1-C6)алкила, или R6 и R7, или R8 и R9, вместе с атомом азота, к которому они присоединены, образуют пирролидиновое, пиперидиновое ...

ИНДИВИДУАЛЬНЫЕ ФОРМЫ ЭНАНТИОМЕРОВ, А ТАКЖЕ ИХ СМЕСИ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ ПРОТИВОСУДОРОЖНЫМ ДЕЙСТВИЕМ

... 1. Индивидуальные формы энантиомеров, а также их смеси, отличающиеся тем, что преобладает один энантиомер карбаматов 2-фенил-1,2-этандиолов, представленных структурной формулой (I), где, что фенильное кольцо содержит в качестве заместителей от одного до пяти атомов галогена, выбранного из фтора, хлора, брома или иода, и R1 и R2 представляют собой функциональные группы, выбранные из водорода и линейной или разветвленной алкильной группы, содержащей от одного до четырех атомов углерода, по возможности, замещенных фенильной группой с заместителями, выбранными из группы, состоящей из водорода, галогена, алкила, алкилокси, амино, нитро и циано. 2. Вещество по п. 1, отличающееся тем, что содержание одного энантиомера составляет около 90% или более. 3. Вещество по п. 1, отличающееся тем, что содержание одного диантиомера составляет около 98% или более. 4. Фармацевтическая композиция для лечения расстройств центральной нервной системы, которая содержит в качестве активного ингредиента эффективное ...

Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to genetic abnormalities

The present invention relates to the use of cannabidiol (CBD) for the treatment of epileptic seizures associated with rare epilepsy syndromes that are treated are those which are experienced in patients diagnosed with a mutation in the PURA gene which encodes for the Pur-alpha (PURα) protein. In a further embodiment the types of seizures include tonic, atonic, and focal seizures with secondary generalisation. Preferably the CBD comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. Where the CBD is given concomitantly with one or more other anti-epileptic drugs (AED) including levetiracetam, clobazam or rufinamide. Preferably the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day. Preferably the CBD used is in the form of a botanically derived purified CBD, but a synthetically produced CBD can alternatively be used. A method of treating seizures with CBD is also disclosed.

Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to structural abnormalities of the brain

The present invention relates to the use of cannabidiol (CBD) for the treatment of epileptic seizures associated with Cortical Dysplasia and Cortical Brain Malformation. In a further embodiment the types of seizures include tonic, atonic, and focal without impairment. Preferably the CBD comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. Where the CBD is given concomitantly with one or more other anti-epileptic drugs (AED) including valproic acid, levetiracetam, clobazam, rufinamide, zonisamide or vigabatrin. Preferably the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day. Preferably the CBD used is in the form of a botanically derived purified CBD, but a synthetically produced CBD can alternatively be used. A method of treating seizures with CBD is also disclosed.

Androstane and pregnane series for allosteric modulations of gaba receptor.

Methods, compositions, and compounds for modulating the gaba receptor-chloride ionophore complex to alleviate stress, anxiety, seizures, mood disorders, pms and ond and to induce anesthesia.

Androstane and pregnane series for allosteric modulations of gaba receptor

Pharmaceutical compositions containing of the dérivésd' azetidine, new derivatives of azetidine and their preparation.

Heterocyclic substituted piperazines for the treatment of schizophrenia.

Androstane and pregnane series for allosteric modulations of gaba receptor

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

Novel bridged cyclic amino acids as pharmaceutical agents

Novel substituted cyclic amino acids as pharmaceutical agents

49 HUMAN SECRETED PROTEINS

The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

EXPRESSION CASSETTE FOR PERSISTENCE OF EXPRESSION OF A GENE OF INTEREST IN MUSCLE CELLS

The present invention concerns the use of a nucleic acid fragment comprising a portion of at least 100 contigous nucleotide bases which portion has a sequence the same as, or homologous to a portion of corresponding length of the sequence as set out in SEQ ID NO: 1 starting at nucleotide approximately 1 and ending at nucleotide approximately 16879 or the same as, or homologous to a portion of the corresponding length of the sequence complementary to said SEQ ID NO: 1 within the specified positions, for improving the persistence of transfected cells expressing one or more gene(s) of interest operably linked to said acid nucleic fragment. The invention also relates to an expression cassette for the expression of one or more gene(s) of interest which expression is controlled by one or more control sequence(s) and a nucleic acid fragment as defined above. The present invention also provides a vector containing said expression cassette and a eukaryotic host cell containing said expression cassette ...

PHARMACEUTICAL COMPOSITIONS, CONTAINING DERIVATIVES OF AZETIDINE, NEW DERIVATIVES OF AZETIDINE AND THEIR PRODUCTION

NOVEL BRIDGED CYCLIC AMINO ACIDS AS PHARMACEUTICALLY ACCEPTABLE AGENTS

Bis-arylsulfones

置換された４−アミノシクロヘキサン誘導体

(S)-α-ФЕНИЛ-2-ПИРИДИНЭТАНАМИН И ЕГО СОЛЬ С НЕОРГАНИЧЕСКИМИ КИСЛОТАМИ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ЛЕКАРСТВЕННЫЙ ПРЕПАРАТ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ СУДОРОГ

Изобретение относится к (S)-α-фенил-2-пиридинэтанамину и его солям с неорганическими кислотами (I), которые обладают противосудорожной активностью (ЕД50 в дозе 3,7 мг/кг). Изобретение относится к лекарственному препарату, обладающему противосудорожным действием, который содержит вещество (I) в эффективном количестве и фармацевтически приемлемые добавки. Изобретение относится к способу лечения судорог путем введения терапевтически эффективной дозы соединения (I). Изобретение относится также к способу получения (I), который заключается в обработке рацемического α-фенил-2-пиридинэтанамина хиральной кислотой с последующим селективным осаждением диастереомерной соли. 4 с. и 4 з.п.ф-лы, 1 ил.

Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to genetic abnormalities

The use of cannabidiol (CBD) for the treatment of epileptic seizures associated with rare epilepsy syndromes, the seizures treated are in patients diagnosed with a protocadherin 19 (PCDH19) mutation. In a further embodiment the types of seizures include tonic-clonic seizures. Preferably the CBD comprises greater than 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. Where the CBD is given concomitantly with one or more other anti-epileptic drugs (AED) including levetiracetam, clobazam, topiramate, gabapentin and phenytoin. Preferably the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day. Preferably the CBD used is in the form of a botanically derived purified CBD, but a synthetically produced CBD can alternatively be used.

AND RUST ON AND PREGNANSERIEN FOR THE ALLOSTERI MODULATION OF THE GABA RECEPTOR

BENZOXAZEPINDERIVATE AND THEIR USE AS STIMULATOREN OF THE AMPA RECEPTOR

AZETIDINDERIVATE ABSTENTIONS PHARMACEUTICAL COMPOSITIONS, THE AZETIDINDERIVATE AND THEIR PRODUCTION

VERB-MOVED CYCLIC AMINO ACIDS AS PHARMACEUTICAL MEANS

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

Pharmaceutical compositions containing azetidine derivatives, novel azetidine derivatives and preparation thereof

Benzoxazepine derivatives and their use as AMPA receptor stimulators

Bis-arylsulfones

Protein-bound cannabinoid compositions

Embodiments of the invention relate to methods for the manufacture of a protein-bound cannabinoid, comprising: obtaining a cannabinoid or cannabis in a form selected from the group consisting of cannabis smoke, cannabis vapor, cannabinoid solution and cannabis extract, and combining the cannabis smoke, vapor, cannabinoid solution or cannabis extract with an aqueous solution or suspension comprising a plasma protein to form a protein-bound cannabinoid. Further embodiments relate to aqueous solutions comprising a plasma protein-bound cannabinoid and pharmaceutical compositions comprising cannabinoids bound to plasma protein.

BIS-ARYLSULFONES

The present invention provides pharmaceutically active compounds useful for the treatment of diseases or disorders of the central nervous system.

Novel Substituted Cyclic Amino Acids as Pharmaceutical Agents

Androstane and Pregnane Series Compounds for Allosteric Modulation of GABA Receptor

A PHARMACEUTICAL COMPOSITION CONTAINING AZETIDINE DERIVATIVES, AZETIDINE DERIVATIVES AND PREPARATION THEREOF

METHOD FOR TREATING PATIENTS WITH COMPLICATED FORMS OF MIGRAINE

CYCLIC AMINO ACIDS DERIVATIVES, PHARMACEUTICAL COMPOSITION BASED THEREON AND METHOD FOR TREATING EPILEPSY, FAINTLESS ATTACKS, HYPOKINESIA, CRANIAL DISORDERS, NEUROGENERATIVE OR NEUROPATHOLOGICAL DISORDERS, DEPRESSION, ANXIETY AND PAIN

ARYL FUSED AZAPOLYCYCLIC COMPOUNDS

This invention is directed to compounds of formula (1) and their pharmaceutically acceptable salts, wherein R1, R2, and R3 are as defined herein; intermediates for the synthesis of such compounds; and methods of using such compounds in the treatment of nicotine addiction/withdrawal and CNS disorders.

USE OF CANNABIDIOL IN THE TREATMENT OF SEIZURES ASSOCIATED WITH RARE EPILEPSY SYNDROMES RELATED TO GENETIC ABNORMALITIES

ПРОИЗВОДНЫЕ БЕНЗОКСАЗЕПИНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ СТИМУЛЯТОРОВ РЕЦЕПТОРА АМРА

Настоящее изобретение относится к органической химии, конкретно к производным бензоксазепина. Описываются производное бензоксазепина общей формулы I где Х представляет собой СО или SO2; R1, R2, R3 и R4 независимо выбраны из Н, (С1-4)алкила, (С1-4 )алкилокси, (С1-4)алкилокси(С1-4)алкила, CF3, галогена, нитро, циано, NR8R9, NR8COR10 и CONR8R9; R5, R6 и R7 независимо представляют собой Н или (С1-4)алкил; R8 и R9 независимо представляют собой Н или (С1-4)алкил; или R8 и R9 вместе с атомом азота, к которому они присоединены, образуют 5- или 6-членное насыщенное гетероциклическое кольцо, необязательно содержащее дополнительный гетероатом, выбранный из О, S или NR11; R10 представляет собой (С1-4)алкил; R11 представляет собой (С1-4)алкил; А представляет собой остаток 4-7-членного насыщенного гетероциклического кольца, необязательно содержащего атом кислорода, где кольцо необязательно замещено 1-3 заместителями, выбранными из (С1-4)алкила, (С1-4)алкилокси, гидрокси, галогена и оксо; или к его фармацевтически ...

Средство, обладающее противосудорожной активностью

Изобретение относится к медицине и фармацевтике. Предложено применение ацетоновой фракции сухого хлороформного экстракта из побегов Empetrum nigrum L. в качестве противосудорожного средства. Получение ацетоновой фракции осуществляется путем двукратной экстракции кипящим хлороформом в круглодонной колбе с обратным холодильником при соотношении сырье : экстрагент - 1:10. Объединенные экстракты упаривают досуха в ротационном испарителе. Трехкратно экстрагируют сухой хлороформный экстракт ацетоном при комнатной температуре и постоянном перемешивании в соотношении экстракт : экстрагент - 1:10. Объединенный ацетоновый экстракт упаривают в ротационном испарителе до 1/3 объема и сушат конвекционно. Технический результат: выраженная противосудорожная активность средства, сравнимая с карбамазепином, при этом увеличивая продолжительность жизни экспериментальных животных на моделях стрихниновых и коразоловых судорог на 54% и 85% соответственно, выживаемость экспериментальных животных составила 20% ...

VERBRÜCKTE ZYKLISCHE AMINOSÄUREN ALS PHARMAZEUTISCHE MITTEL

Use of cannabinoids in the treatment of epilepsy

Cannabidiolic acid (CBDA) for use in the treatment of epilepsy, preferably where the epilepsy is a generalised epilepsy characterised by tonic-clonic seizures. Preferably the CBDA is in the form of a highly purified extract of cannabis such that the CBDA is present at greater than 98% of the total extract (w/w) and comprises less than 1% (w/w) tetrahydrocannabinol (THC) or tetrahydrocannabinol acid (THCA). The CBD may be synthetically produced. The CBDA may be used with cannabidiol (CBD) preferably where the CBDA:CBD ratio is in the range from 9:1 to 1:9 (CBDA:CBD). Preferably the CBD is used at a dose of from 1mg-100mg.

Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to structural abnormalities of the brain

The present invention relates to the use of cannabidiol (CBD) for the treatment of epileptic seizures associated with Ohtahara Syndrome or Ohtahara Syndrome secondary to a mutation of the aminoacyl tRNA synthetase complex interacting multifunctional protein 1 (AIMP1) gene. In a further embodiment the types of seizures include tonic, atonic, myoclonic, absence and focal seizures with impairment. Preferably the CBD comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. Where the CBD is given concomitantly with one or more other anti-epileptic drugs (AED) including levetiracetam, clobazam, rufinamide, zonisamide or vigabatrin. Preferably the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day. Preferably the CBD used is in the form of a botanically derived purified CBD, but a synthetically produced CBD can alternatively be used. A method of treating seizures with CBD is also disclosed.

PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF DISTURBANCES OF THE ZNS OR OTHER ILLNESSES

CYCLIC AMINO ACID AS PHARMACEUTICAL ACTIVE SUBSTANCES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

USE FROM PHTHALAZIN DERIVATIVES TO THE TREATMENT OF NEURODEGENERATIVE DISEASES

BENZOXAZEPINE DERIVATIVES AND THEIR USE AS AMPA RECEPTOR STIMULATORS

The present invention relates to benzoxazepine derivative having the general formula I, wherein X represents CO or SO2; R1, R2, R3 and R4 are independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, halogen, nitro, cyano, NR8R9, NR8COR10, and CONR8R9, R5, R6 and R7 are independently H or (C1-4)alkyl; R8 and R9 are independently H or (C1-4)alkyl; or R8 and R9 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR11; R10 is (C1-4)alkyl; R11 is (C1-4)alkyl; A represents the residue of a 4-7 membered saturated heterocyclic ring, optionally containing an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C1-4)alkyl, (C1-4)alkyloxy, hydroxy, halogen and oxo; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, and to the use of ...

SECRETED PROTEINS

The invention provides human secreted proteins (SECP) and polynucleotides which identify and encode SECP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of SECP.

ENANTIOMERIC 1-PHENYL-2-(2-PYRIDINYL) ETHYLAMINE FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS

... 2133427 9320052 PCTABS00027 (S)-.alpha.-phenyl-2-pyridineethanamine, and its pharmaceutically acceptable derivatives, are useful in the treatment of neurodegenerative disorders, and exhibit linear pharmacokinetics.

NOVEL SUBSTITUTED CYCLIC AMINO ACIDS AS PHARMACEUTICAL AGENTS

Novel substituted cyclic amino acids of formula (I) are disclosed and are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, and neuropathological disorders. Processes for the preparation and intermediates useful in the preparation are also disclosed.

PHARMACEUTICAL COMPOSITIONS CONTAINING OF DERIVED From AZETIDINE, the NOUVEAUXDERIVES Of AZETIDINE AND THEIR PREPARATION

EXPRESSION CASSETTE FOR PERSISTENCE OF EXPRESSION OF A GENE OF INTEREST IN MUSCLE CELLS

The present invention concerns the use of a nucleic acid fragment comprising a portion of at least 100 contigous nucleotide bases which portion has a sequence the same as, or homologous to a portion of corresponding length of the sequence as set out in SEQ ID NO: 1 starting at nucleotide approximately 1 and ending at nucleotide approximately 16879 or the same as, or homologous to a portion of the corresponding length of the sequence complementary to said SEQ ID NO: 1 within the specified positions, for improving the persistence of transfected cells expressing one or more gene(s) of interest operably linked to said acid nucleic fragment. The invention also relates to an expression cassette for the expression of one or more gene(s) of interest which expression is controlled by one or more control sequence(s) and a nucleic acid fragment as defined above. The present invention also provides a vector containing said expression cassette and a eukaryotic host cell containing said expression cassette ...

TRIAZOLOPYRIMIDINOL COMPOUNDS AND SALTS THEREOF

L'invention concerne du 7-[1-(4-chlorophenoxy)éthyl]-1,2,4-triazolo[1,5-a]pyrimidin-5-ol isolé ainsi que ses sels pharmaceutiquement acceptables sous forme d'énantiomères individuels et leurs mélanges, y compris le mélange racémique. L'invention concerne également des formulations pharmaceutiques contenant ce composé et l'utilisation de ce composé dans le traitement de crises, de troubles neurologiques tels que l'épilepsie et/ou de lésions liées à une altération neurologique telle que les crises d'apoplexie, les lésions cérébrales, les traumatismes crâniens et les hémorragies cérébrales.

USE OF CANNABIDIOL IN THE TREATMENT OF SEIZURES ASSOCIATED WITH RARE EPILEPSY SYNDROMES RELATED TO STRUCTURAL ABNORMALITIES OF THE BRAIN

The present invention relates to the use of cannabidiol (CBD) for the treatment of seizures associated with rare epilepsy syndromes. In particular the seizures associated with rare epilepsy syndromes that are treated are those which are experienced in patients diagnosed with Heterotopia. In a further embodiment the types of seizures include tonic, tonic-clonic, atonic, absence and focal seizures without impairment. Preferably the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day.

DERIVATIVES OF AMINOALKANOLS, METHOD OF OBTAINING OF AMINOALKANOLS AND THEIR USE

The subject of the invention is a group of new derivatives of aminoalkaπols, more specifically [(phenoxy)alkyl]aminoalkanols and [(phenoxy)acyl)aminoalkanols, their method of obtaining and their use for production of a medicine which is used in the prophylaxis, prevention and/or treatment of diseases or symptoms having neurological background and for production of a medicine with anticonvulsant activity, which is used in seizures of various origin, also in the limbic system, in myoclonic or sound-induced seizures, in psychomotor epilepsy, as well as in relieving neuropathic or inflammatory pain.

СТЕРОИДНЫЕ СОЕДИНЕНИЯ (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ЛЕЧЕНИЯ НЕРВНЫХ РАССТРОЙСТВ (ВАРИАНТЫ) И СПОСОБ ИНДУКЦИИ АНЕСТЕЗИИ У ЖИВОТНОГО

Описываются стероидные соединения общей формулы I, где a) R4 - 3'-метил-бут-3'-ен-1'-инил или циклопропилэтинил, R5 - метил, R6 - ацетил, штриховая линия означает одинарную связь; б) R4 - трифторметил, R5 - метил, R6 - ацетил, штриховая линия означает одинарную или двойную связь и в случае, когда связь одинарная, R6 - гидроксиацетил, a R5 - водород, R4 может означать фторметил; в) R4 - этинил, R5 - метил, R6 - гидроксиметил или гидроксиацетил, штриховая линия означает одинарную связь, или их физиологически приемлемые сложные 21-эфиры, 3,20-диэфиры или 3,21-диэфиры, или где a) R6 - гидроксиацетил, R5 - водород в случае, когда R4 - трифторметил и соединение представлено в виде 21-гемисукцината натрия; б) R6 - гидроксиацетил, R5 - метил, а R4 принимает следующие значения: водород, в случае, когда соединение представлено в виде бисгемисукцината; этинил, в случае 21-гемисукцината; трифторметил в случае 21-гемифумарата натрия, метил 21-сукцината, 21-пропионата; и в) R4 - метил, R5 - метил, R6 ...

ЭНАНТИОМЕРНЫЙ 1-ФЕНИЛ-2-(2-ПИРИДИНИЛ) ЭТИЛАМИН ДЛЯ ЛЕЧЕНИЯ НЕЙРОДЕГЕНЕРАТИВНЫХ РАССТРОЙСТВ

... (S)-альфа-фенил-2-пиридинэтанамин и его фармацевтически приемлемые производные, полезные при лечении нейродегенеративных расстройств и проявляющие линейные фармакокинетические свойства.

BENZOXAZEPINDERIVATE UND DEREN VERWENDUNG ALS STIMULATOREN DES AMPA-REZEPTORS

Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to genetic abnormalities

The present invention relates to the use of cannabidiol (CBD) for the treatment of epileptic seizures associated with rare epilepsy syndromes that are treated are those which are experienced in patients diagnosed with a mutation in CHRNA4 gene which encodes the α4 subunit of a neuronal nicotinic acetylcholine receptor (nAChR). In a further embodiment the types of seizures include tonic-clonic, atonic, myoclonic, and absence. Preferably the CBD comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. Where the CBD is given concomitantly with one or more other anti-epileptic drugs (AED), the AED is rufinamide. Preferably the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day. Preferably the CBD used is in the form of a botanically derived purified CBD, but a synthetically produced CBD can alternatively be used. A method of treating seizures with CBD is also disclosed.

The phytocannabinoid cannabidivarin (CBDV) for use in the treatment of epilepsy

ARYL ANNELLIERTE AZAPOLYZYKLI CONNECTIONS

ENANTIOMERE 1-PHENYL-2 (2-PYRIDINYL) ETHYL AMINE FOR the TREATMENT of NEURODEGENERATIVE DISTURBANCES

Pharmaceutical compositions containing azetidine derivatives, novel azetidine derivatives and preparation thereof

Methods of treating epilepsy or status epilepticus

Described herein are methods of treating epilepsy or status epilepticus, e.g., convulsive status epilepticus, e.g., early status epilepticus, established status epilepticus, refractory status epilepticus, super-refractory status epilepticus, e.g., super-refractory generalized status epilepticus; non- convulsive status epilepticus, e.g., generalized status epilepticus, complex partial status epilepticus; generalized periodic epileptiform discharges; periodic lateralized epileptiform discharges; a seizure, e.g., acute repetitive seizures, cluster seizures, the method comprising administering to the subject a neuroactive steroid.

Protein-bound cannabinoid compositions

Embodiments of the invention relate to methods for the manufacture of a protein-bound cannabinoid, comprising: obtaining a cannabinoid or cannabis in a form selected from the group consisting of cannabis smoke, cannabis vapor, cannabinoid solution and cannabis extract, and combining the cannabis smoke, vapor, cannabinoid solution or cannabis extract with an aqueous solution or suspension comprising a plasma protein to form a protein-bound cannabinoid. Further embodiments relate to aqueous solutions comprising a plasma protein-bound cannabinoid and pharmaceutical compositions comprising cannabinoids bound to plasma protein.

Process for the purification of eslicarbazepine acetate

The present invention relates to the purification and particle size of eslicarbazepine acetate. The present invention also relates to the physical characteristics of solid state eslicarbazepine acetate, and pharmaceutical compositions containing the same.

Biphenylacetamide derivative

The present invention provides a compound of formula (I) or a salt thereof, wherein R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, bromine atom, C 1-6 alkyl, C 1-6 alkoxy substituted with fluorine atom, and others; R 4 and R 5 are independently selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, C 1-6 alkyl, C 1-6 alkoxy substituted with fluorine atom, and others; R 6 and R 7 are independently selected from the group consisting of hydrogen atom, fluorine atom, methyl, ethyl, hydroxy group, and others; and R 8 and R 9 are independently selected from the group consisting of hydrogen atom, C 1-6 alkyl, and others, which is useful as an agent for treating or preventing various types of epilepsy including partial seizures and/or generalized seizures.

Ethanamine Compounds and Methods of Using the Same

(S)-2-methyl- 1 -phenyl-2-(pyridin-2-yl)propan-1-amine, pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the same, uses of said compound or salt for therapy of depression and other conditions, and methods of treating depression and other conditions by administering said compound or salt.

Novel sulfamides exhibiting neuroprotective action and methods for use thereof

Pharmaceutical compositions of the invention include sulfamide derivatives having a disease-modifying action in the treatment of diseases associated with excitotoxicity and accompanying oxidative stress that include epilepsy, Alzheimer's disease, and any neurodegenerative disease involving glutamate toxicity.

Pharmaceutical formulation containing phenytoin sodium and magnesium stearate

The present invention relates to a novel pharmaceutical formulation comprising phenytoin sodium, a high amount of magnesium stearate, and a low level of a hydrophilic polymer such as a methocel, and a method of preparing the same by blending.

Composition and method for compounded therapy

The present embodiments relate to topically delivered compounded medications. A transdermal cream may provide the effective topical administration of multiple medications simultaneously. The transdermal cream may include low concentrations of local anesthetics, a NSAID, an anticonvulsant, and/or other active ingredients. For instance, the transdermal cream may include lidocaine, prilocaine, meloxicam, and lamotrigine and/or topiramate. Alternatively, the transdermal cream may include a lidocaine/prilocaine base cream to which is added a fine powder of one or more ground up medications to form a compounded medication. The compounded medication in powder form may be generated from grinding up tablets of NSAIDs, anticonvulsants, nerve depressants, antidepressants, muscle relaxants, NMDA receptor antagonists, opiate or opioid agonists, and/or other agents. The compounded medication in powder form may include meloxicam, lamotrigine, topiramate, and/or other active ingredients. In another aspect, the present embodiments relate to methods of compounding medications and transdermal creams or gels.

Liquid ganaxolone formulations and methods for the making and use thereof

In certain embodiments, the invention is directed to composition comprising stable particles comprising ganaxolone, wherein the volume weighted median diameter (D50) of the particles is from about 50 nm to about 500 nm.

Direct compression tablets of otilonium

This invention is related to direct compression of otilonium or its pharmaceutically acceptable salt having perfect powder flowability, good tablet weight distribution and no sticking to the punches.

METHODS OF TREATING SEIZURE DISORDERS AND PRADER-WILLI SYNDROME

Methods of treating a seizure disorder with (1S,3S)-3-amino-4-(difluoromethylidene)cyclopentane-1-carboxylic acid, or (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (KT-II-115), or a pharmaceutically acceptable salt of any of the preceding, are provided. The methods provide therapeutic compositions that may be used to improve one or more symptoms of a seizure disorder. Methods of treating Prader-Willi syndrome with (1S,3S)-3-amino-4-(difluoromethylidene)cyclopentane-1-carboxylic acid, or (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (KT-II-115), or a pharmaceutically acceptable salt of any of the preceding, are provided. The methods provide therapeutic compositions that may be used to improve one or more symptoms of Prader-Willi syndrome. 1. A method of treating a seizure disorder comprising administering to a subject with the seizure disorder (1S ,3S)-3-amino-4-(difluoromethylidene)cyclopentane-1-carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of from 0.01 mg to 500 mg.2. The method of treating a seizure disorder according to claim 1 , wherein the total amount of (1S claim 1 ,3S)-3-amino-4-(difluoromethylidene)cyclopentane-1-carboxylic acid or a pharmaceutically acceptable salt thereof administered to the subject in a twenty-four hour period is between 1 mg and 500 mg.3. The method of treating a seizure disorder according to claim 1 , wherein the seizure disorder is selected from the group consisting of epilepsy claim 1 , epilepsy with generalized tonic-clonic seizures claim 1 , epilepsy with myoclonic absences claim 1 , frontal lobe epilepsy claim 1 , temporal lobe epilepsy claim 1 , Landau-Kleffner Syndrome claim 1 , Rasmussen's syndrome claim 1 , Dravet syndrome claim 1 , Doose syndrome claim 1 , CDKL5 disorder claim 1 , infantile spasms (West syndrome) claim 1 , tuberous sclerosis complex claim 1 , juvenile myoclonic epilepsy (JME) claim 1 , vaccine-related encephalopathy claim 1 , ...

Expression vectors comprising engineered genes

The invention provides expression vectors, nucleic acids, vector particles and methods of treatment involving these vector particles, comprising an engineered KCNA1 gene encoding an edited Kv1.1 potassium channel, as well as methods of confirming the presence of engineered KCNA1 mRNA in a cell. The features of the engineered KCNA1 gene combine to advantageously enhance the translation and activity of the Kv1.1 protein and improve detection of KCNA1 gene expression in a cell and can be used for example in the treatment of epilepsy and similar neurological disorders.

METABOLISM RESISTANT FENFLURAMINE ANALOGS AND METHODS OF USING THE SAME

Metabolism-resistant fenfluramine analogs are provided. The subject fenfluramine analogs find use in the treatment of a variety of diseases. For example, methods of treating epilepsy by administering a fenfluramine analog to a subject in need thereof are provided. Also provided are methods of suppressing appetite in a subject in need thereof. Pharmaceutical compositions for use in practicing the subject methods are also provided. 8. The method of , wherein the compound is a compound according to one of -.9. The method of claim 7 , further comprising co-administering to the subject an antiepileptic agent.11. (canceled) Pursuant to 35 U.S.C. § 119 (e), this application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 62/271,168, filed Dec. 22, 2015, the disclosure of which application is hereby incorporated by reference herein in its entirety.This invention relates generally to the field of compounds structurally related to the amphetamine drug fenfluramine and their use in the treatment of neurological related diseases.Fenfluramine is an amphetamine drug that was once widely prescribed as an appetite suppressant to treat obesity. Fenfluramine is devoid of the psychomotor stimulant and abuse potential of D-amphetamine and interacts with the 5-hydroxytryptamine (serotonin, 5-HT) transporters to release 5-HT from neurons. Fenfluramine has been investigated for anticonvulsive activity in the treatment of Dravet Syndrome, or severe myoclonic epilepsy in infancy, a rare and malignant epileptic syndrome. This type of epilepsy has an early onset in previously healthy children.Anorectic treatment with fenfluramine has been associated with the development of cardiac valvulopathy and pulmonary hypertension, including the condition cardiac fibrosis which led to the withdrawal of fenfluramine from world-wide markets. Interaction of fenfluramine's major metabolite norfenfluramine with the 5-HT2B receptor is associated with heart valve hypertrophy. In ...

USE OF CANNABINOLIDS IN THE TREATMENT OF EPILEPSY

The present invention relates to the use of cannabidiol (CBD) in the treatment of epilepsy which results from mutation of the GRIN2A gene. The CBD used is in the form of a highly purified extract of such that the CBD is present at greater than 98% of the total extract (w/w) and the other components of the extract are characterised. In particular the cannabinoid tetrahydrocannabinol (THC) is present in an amount of from 0.02 to 0.1% (w/w). In an alternative embodiment the CBD may be in a synthetic form. In use the CBD may also be used concomitantly with one or more other anti-epileptic drugs (AED). The CBD may be formulated for administration separately, sequentially or simultaneously with one or more AED or the combination may be provided in a single dosage form. Where the CBD is formulated for administration separately, sequentially or simultaneously it may be provided as a kit or together with instructions to administer the one or more components in the manner indicated. It may also be used as the sole medication, i.e. as a monotherapy. 1. Cannabidiol (CBD) for use in the treatment of epilepsy associated with GRIN2A mutation.2. Cannabidiol (CBD) for use according to claim 1 , for the treatment of non-seizure symptoms in epilepsy associated with GRIN2A mutation.3. CBD for use according to any of the preceding claims claim 1 , wherein the epilepsy is a treatment resistant epilepsy (TRE).4. CBD for use according to any of the preceding claims claim 1 , wherein the CBD is for use in combination with one or more concomitant anti-epileptic drugs (AED).5cannabis. CBD for use according to any of the preceding claims claim 1 , wherein the CBD is present as a highly purified extract of which comprises at least 98% (w/w) CBD.6. CBD for use according to claim 5 , wherein the extract comprises up to 0.1% (w/w) THC.7. CBD for use according to claim 6 , wherein the THC is present at a concentration of between 0.02 and 0.1% (w/w).8. CBD for use according to or claim 6 , wherein ...

STEROID DERIVATIVE REGULATORS, METHOD FOR PREPARING THE SAME, AND USES THEREOF

Steroid derivative regulators, a method for preparing the same, and uses thereof are described. Specifically, a compound as shown in formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and uses thereof as a regulator of GABA A receptor for treating depression, convulsion, Parkinson's disease, and nervous system diseases are described, wherein the substituents of the formula (I) are as defined in the description. 16. The compound of formula (I) claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 , wherein Rselected from the group consisting of hydrogen atom claim 5 , cyano claim 5 , halogen claim 5 , nitro claim 5 , Calkyl claim 5 , Calkynyl claim 5 , Calkoxy claim 5 , Chaloalkyl claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , 5 to 10 membered heterocyclyl claim 5 , 5 to 10 membered heteroaryl claim 5 , —(CH) claim 5 ,10R claim 5 , —(CH)SR claim 5 , —(CH)C(O)R claim 5 , —(CH)C(O)NRR claim 5 , —(CH)C(O)ORand —(CH)S(O)R claim 5 , wherein the Calkyl claim 5 , Calkoxy claim 5 , Chaloalkyl claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , wherein the 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of hydrogen atom claim 5 , Calkyl claim 5 , halogen claim 5 , cyano claim 5 , hydroxy claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl;{'sub': 23', '24', '1-6, 'Rand Rare each independently selected from the group consisting of hydrogen atom, Calkyl and 3 to 8 membered heterocyclyl.'}17. The compound of formula (I) claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 ,wherein:{'sub': 2', '2', '2', '2', '2, 'Z is selected from the group consisting of —CH—, —CHNH—, —CHO—, —CH—, —NH— and —NHSO—;'}{'sub': 3a', '1-6', '1-6', '1-6 ...

Use of cannabinoids in the treatment of epilepsy

The present invention relates to the use of cannabidiol (CBD) in the treatment of focal seizures. In one embodiment the patients suffering from focal seizures are children and young adults. CBD appears particularly effective in reducing focal seizures in patients suffering with etiologies that include: Lennox-Gastaut Syndrome; Tuberous Sclerosis Complex; Dravet Syndrome; CDKL5; Neuronal ceroid lipofuscinoses (NCL); febrile infection related epilepsy syndrome (FIRES); Aicardi syndrome and brain abnormalities in comparison to other seizure types. Significantly CBD additionally is very effective in the reduction of a sub-type of focal seizures, focal seizures with impairment.

Process and intermediates for the preparation of perampanel

The present invention describes a process for the synthesis of 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-di-hydro-pyridin-2-one (Perampanel) represented by the structure of formula (1), and salts thereof, especially salts with pharmaceutically acceptable acids. The present invention further relates to certain intermediates formed and/or used in such process.

Use Of [(1R)-1-(2-Chlorophenyl)-2-(Tetrazol-2-YL)Ethyl] Carbamate In Combination Therapy

The present disclosure provides combination therapy using [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] carbamate (cenobamate) and one or more antiepileptic drugs for the prevention or treatment of a neurological disorder such as epilepsy. 1. A method for treating a patient who is suffering from epilepsy with co-administering a therapeutically effective amount of (i) [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] carbamate (cenobamate) or a pharmaceutically acceptable salt thereof and (ii) one or more antiepileptic drugs , said method comprising:modifying the therapeutically effective amount of the antiepileptic drug to adjust AUC of the antiepileptic drug obtained after the co-administration having at least 5% difference to the level of AUC obtained after the administration of antiepileptic drug to the patient without cenobamate or a pharmaceutically acceptable salt thereof,wherein the therapeutically effective amount of cenobamate or a pharmaceutically acceptable salt thereof is from about 100 mg/day to about 400 mg/day.2. The method according to claim 1 , wherein the antiepileptic drug is selected from the group consisting of carbamazepine claim 1 , lamotrigine claim 1 , phenobarbital and phenytoin.3. The method according to claim 1 , wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:(1) administering cenobamate to the patient about 12.5 mg once daily for about two weeks;(2) then administering cenobamate to the patient about 25 mg once daily for two weeks;(3) then administering cenobamate to the patient about 50 mg once daily for about two weeks; and(4) then increasing the dose in about bi-weekly increments by no more than about 50 mg once daily to a therapeutically effective amount.4. The method according to claim 1 , wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:(1) administering cenobamate to the patient about 50 mg once daily for about two ...

CANNABIDIOL PREPARATIONS AND ITS USES

Cannabidiol (CBD) is a cannabinoid designated chemically as 2-[(1R,6R)-3-Methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol. Its empirical formula is CHOand its molecular weight is 314.46. CBD is a cannabinoid that naturally occurs in the L. plant. CBD is a white to pale yellow crystalline solid which is insoluble in water and soluble in organic solvents. The present invention encompasses the surprising recognition that certain CBD preparations which are prepared from a botanical origin are more effective in treating diseases or disorders than preparations of CBD which are synthetic or purified to the extent no other impurities in the form of other cannabinoids are present. Prior CBD compositions have been prepared such that no psychoactive components, e.g., tetrahydrocannabinol (THC), remain in the final CBD preparation. Surprisingly, the absence of such minor impurities reduces the efficacy of CBD treatment. Such CBD preparations are characterized by chemical components and/or funtional properties that distinguish them from prior CBD compositions. One or more components of the preparations described herein provide an unexpectedly synergistic effect when utilized in combination. 1. A cannabidiol (CBD) preparation comprising greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids , wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4) , and wherein the THC is present as a mixture of trans-THC and cis-THC.2. The CBD preparation of claim 1 , comprising not more than 1.5% (w/w) THC based on total amount of cannabinoid in the preparation.3. The CBD preparation of claim 1 , comprising about 0.01% to about 0.1% (w/w) THC based on total amount of cannabinoid in the preparation.4. The CBD preparation of claim 6 , comprising about 0.02% to about 0.05% (w/w) THC based on total amount ...

PHARMACEUTICAL COMBINATION COMPRISING A T-TYPE CALCIUM CHANNEL BLOCKER

The present invention relates to a pharmaceutical combination comprising a first active ingredient which is N-[1-(5-Cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide or a pharmaceutically acceptable salt thereof and a second active ingredient which has an anti-epileptic effect, or a pharmaceutically acceptable salt thereof. 1. A pharmaceutical combination comprising a first active ingredient which is N-[1-(5-Cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide or a pharmaceutically acceptable salt thereof and a second active ingredient which has an anti-epileptic effect , or a pharmaceutically acceptable salt thereof.2. A pharmaceutical combination according to claim 1 , wherein the second active ingredient is selected from the group consisting of 5H-dibenzo[b claim 1 ,f]azepine-5-carboxamide claim 1 , (RS)-3-ethyl-3-methyl-pyrrolidine-2 claim 1 ,5-dione claim 1 , 6-(2 claim 1 ,3-dichlorophenyl)-1 claim 1 ,2 claim 1 ,4-triazine-3 claim 1 ,5-diamine claim 1 , (S)-2-(2-oxopyrrolidin-1-yl)butanamide claim 1 , 10 claim 1 ,11-dihydro-10-oxo-5H-dibenz[b claim 1 ,f]azepine-5-carboxamide claim 1 , 2-propylpentanoic acid claim 1 , N-(5-sulfamoyl-1 claim 1 ,3 claim 1 ,4-thiadiazol-2-yl)acetamide claim 1 , (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide claim 1 , 7-chloro-1-methyl-5-phenyl-1 claim 1 ,5-benzodiazepine-2 claim 1 ,4-dione claim 1 , 5-(2-chlorophenyl)-7-nitro-1 claim 1 ,3-dihydro-1 claim 1 ,4-benzodiazepin-2-one claim 1 , (S)-10-acetoxy-10 claim 1 ,11-dihydro-5H-dibenz[b claim 1 ,f]azepine-5-carboxamide claim 1 , (3-carbamoyloxy-2-phenylpropyl) carbamate claim 1 , 1-(aminomethyl)cyclohexaneacetic acid claim 1 , (R)-2-acetamido-N-benzyl-3-methoxypropanamide claim 1 , 5′-(2-cyanophenyl)-1′-phenyl-2 claim 1 ,3′-bipyridinyl-6′(1′H)-one claim 1 , 5-ethyl-5-phenyl-1 claim 1 ,3-diazinane-2 claim 1 ,4 claim 1 ,6-trione claim 1 , 5 claim 1 ,5-diphenylimidazolidine-2 claim 1 , ...

METHODS FOR TREATING AND FOR INHIBITING PROGRESSION OF SEIZURES

Methods for treating seizures and for inhibiting progression of a focal seizure to a generalized seizure by administering extracranially a Clostridial derivative are described. 1. A method for treating seizures associated with a seizure disorder or for treating aura seizure symptoms , comprising:administering to a subject with a seizure disorder or aura seizure symptoms a Clostridial derivative in an amount effective for treating seizures, the Clostridial derivative administered extracranially to at least one administration site.2. The method of claim 1 , wherein administering comprises administering by extramuscular injection claim 1 , subcutaneous injection claim 1 , subdermal injection or intradermal injection.3. The method of claim 1 , wherein administering comprises administering by injection to the scalp of the subject.4. The method of claim 1 , wherein administering is to more than one administration site.5. (canceled)6. (canceled)7. (canceled)8. The method of claim 1 , wherein the at least one administration site is to an occipital area of the cranium that is innervated by cervical nerves.9. (canceled)10. (canceled)11. The method of claim 1 , wherein the Clostridial derivative is a botulinum neurotoxin.12. (canceled)13. The method of claim 11 , wherein the botulinum neurotoxin is botulinum toxin type A claim 11 , botulinum toxin type B claim 11 , botulinum toxin type C claim 11 , botulinum toxin type D claim 11 , or botulinum toxin type E.14. The method of claim 11 , wherein the botulinum toxin is selected from the group consisting of onabotulinumtoxinA claim 11 , abobotulinumtoxinA claim 11 , incobotulinumtoxinA claim 11 , daxibotulinumtoxinA claim 11 , prabotulinumtoxinA claim 11 , and rimabotulinumtoxinB.15. The method of claim 13 , wherein the botulinum toxin comprises a botulinum neurotoxin complex or a pure toxin.16. (canceled)17. The method of claim 1 , wherein the seizure is a focal onset seizure claim 1 , a myoclonic seizure claim 1 , or a primary ...

PYRIMIDINE COMPOUND

The present invention provides a novel pyrimidine compound represented by Formula [I] and a salt thereof: 2. The compound according to claim 1 , whereinring A is phenyl,L is —O—, andn is 0, or a salt thereof.3. The compound according to claim 1 , wherein m is 0 claim 1 , or a salt thereof.4. The compound according to claim 1 , wherein Ris halogen claim 1 , lower alkynyl claim 1 , lower alkyl or —S-lower alkyl optionally substituted with halogen claim 1 , or a salt thereof.7. A pharmaceutical composition comprising a compound according to or a salt thereof claim 1 , as an active ingredient and pharmaceutically acceptable carrier or excipient.89.-. (canceled)10. A method for treating claim 1 , preventing and/or diagnosing seizure in diseases involving epileptic seizure or convulsive seizure (including multiple drug resistant seizure claim 1 , refractory seizure claim 1 , acute symptomatic seizure claim 1 , febrile seizure and status epilepticus) claim 1 , which comprises administering to a human in need thereof an effective amount of a compound according to or a salt thereof.1112.-. (canceled) The present invention relates to a pyrimidine compound and a salt thereof. The present invention also relates to a medicament having a pyrimidine compound or a salt thereof as an active ingredient and useful for treating, preventing and/or diagnosing seizure and the like in disease involving epileptic seizure or convulsive seizure.The prevalence of epilepsy is about 1% of the population. It is considered a common neurological disorder with about 1 million patients in Japan and a lifetime morbidity rate of 3% to 4%, and it is estimated that tens of thousands of people develop epilepsy every year. About 70% of these patients can control their seizure with existing antiepileptic drugs and pursue their everyday lives without problems, but the remaining 30% of epileptic patients are unable to adequately control their seizure, and are anxious that seizure may occur without warning. ...

ANTIEPILEPTIC TOXIN MARTENTOXIN AND USE THEREOF

The present invention provides uses for the anti-epileptic toxin Martentoxin and derivatives thereof. Specifically, the present invention provides the use of Martentoxin (or MarTX toxin) or an active fragment thereof or a pharmaceutically acceptable salt thereof in preparing a preparation or composition for treating and/or preventing epilepsy. 1. A method of treating epilepsy in a subject in need thereof , comprising administering a composition comprising a MarTX toxin , an active fragment thereof , or a pharmaceutically acceptable salt thereof.2. The method of claim 1 , wherein the epilepsy comprises epilepsy caused by increased excitability of cerebral cortex or epilepsy caused by abnormal excitation of neurons.3. The method of claim 1 , wherein the amino acid sequence of the MarTX toxin is shown as SEQ ID NO: 2 or 3.4. The method of claim 1 , wherein the MarTX toxin comprises the amino acid sequence obtained by substitution claim 1 , deletion claim 1 , alteration claim 1 , insertion claim 1 , or addition of one or more amino acids based on the sequence SEQ ID NO: 2 within the range of maintaining protein activity.5. The method of claim 1 , wherein the MarTX toxin comprises insertion of one or more amino acids at the N terminus or C terminus of the sequence SEQ ID NO: 2 claim 1 , within the range of maintaining protein activity claim 1 , and the number of inserted amino acid residues comprises 1 to 10 claim 1 , preferably 1 to 5 claim 1 , more preferably 1 to 3.6. The method of claim 1 , wherein the composition is a pharmaceutical composition.7. The method of claim 6 , wherein the dosage form of the pharmaceutical composition is an injection.8. The method of claim 6 , wherein the pharmaceutical composition is administered intravenously claim 6 , subcutaneously claim 6 , intramuscularly or intracranially.9. The method of claim 8 , wherein the injection is administered by microinfusion pumps.10. The method of claim 7 , wherein the injection is administered by ...

ORAL ANTI-INFLAMMATORY PEPTIDES TO TREAT EPILEPSY, SEIZURES AND CNS DISORDERS

A method of treating seizures, epilepsy or loss of brain function in an individual comprising the steps of preparing a composition composed of an all-D amino acid peptide and a pharmaceutically acceptable carrier. 1: A method of treatment for epilepsy , seizures , or loss of brain function in a patient with a brain injury comprising the steps of: A is Ser, Thr, Asn, Glu, Ile.', 'B is Ser, Thr, Asp, Asn,', 'C is Thr, Ser, Asn, Arg, Trp,', 'D is Tyr, and', 'E is Thr, Ser, Arg, Gly., 'preparing a composition comprising a D peptide and an acceptable carrier, said D peptide further comprises five contiguous amino acids having the general structure: A-B-C-D-E in whichwherein all amino acids are the D stereoisomeric configuration, and administering said composition to the patient in a therapeutically effective dose, wherein said composition acts to treat epilepsy, seizures, or loss of brain function in the patient.2: The method as defined in wherein said D peptide is TTNYT (SEQ ID NO: 1)4: The method as defined in wherein said composition further comprises an oral pill having anti-inflammatory activity and wherein said peptide in said composition is present in a concentration having a range from 0.05 μg to 1000 μg.5: The method as defined in wherein E may be esterified claim 1 , glycosylated claim 1 , or amidated to enhance tissue distribution and entry into brain.6: The method as defined in wherein said composition further comprises an oral pill having anti-inflammatory activity and wherein said peptide in said composition is present in a concentration having a range from 0.05 μg to 1000 μg.7: The method as defined in claim 6 , wherein said anti-inflammatory activity consists of CCR5 or CCR2 receptor antagonism.8: The method as defined in wherein said anti-inflammatory activity consists of dual CCR5 and CCR2 antagonism.9: The method of disease treatment as defined in wherein said anti-inflammatory activity causes a reduction in inflammatory cytokines selected from: TNFα ...

ANTISENSE OLIGOMERS FOR TREATMENT OF CONDITIONS AND DISEASES

Alternative splicing events in SCN1A gene can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression, and therapeutic agents which can target the alternative splicing events in SCN1A gene can modulate the expression level of functional proteins in Dravet Syndrome patients and/or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition caused by SCN1A, SCN8A or SCN5A protein deficiency. 1. A method of treating a disease or condition associated with a reduced expression or function of Nav1.1 protein encoded by a SCN1A gene in a subject in need thereof by increasing expression of the Nav1.1 protein in a cell of the subject , comprising: introducing a therapeutic agent into the cell of the subject , wherein the therapeutic agent promotes exclusion of a non-sense mediated mRNA decay-inducing exon (NMD exon) from an mRNA in the cell that contains the NMD exon (NMD exon mRNA) and that encodes the Nav1.1 protein , thereby increasing level of processed mRNA encoding the Nav1.1 protein , and increasing the expression of the Nav1.1 protein in the cell of the subject.2. The method of claim 1 , wherein the therapeutic agent(a) binds to a targeted portion of the NMD exon mRNA encoding Nav1.1;(b) modulates binding of a factor involved in splicing of the NMD exon mRNA encoding Nav1.1; or(c) a combination of (a) and (b).3. The method of claim 2 , wherein the targeted portion is within an intron sequence flanking the NMD exon.4. The method of claim 2 , wherein the targeted portion comprises at least one nucleotide or 2 claim 2 , 3 claim 2 , 4 claim 2 , 5 claim 2 , 6 claim 2 , 7 claim 2 , 8 claim 2 , 9 claim 2 , or 10 consecutive nucleotides of the NMD exon.5. The method of claim 2 , wherein the targeted portion is within the NMD exon.6. The method of claim 1 , wherein the disease or condition is associated with a loss-of-function mutation in the SCN1A gene.7. The method of claim 1 , wherein the disease or ...

AMPA RECEPTOR ANTAGONISTS SPECIFIC FOR CALCIUM PERMEABLE AMPA RECEPTORS AND METHODS OF TREATMENT THEREWITH

Antagonists that are specific for calcium permeable AMPA subtype glutamate receptors (CP-AMPARs) which lack the GluA2 subunit and methods utilizing the specific AMPA receptor antagonists to treat disorders and diseases having enhanced CP-AMPAR function or expression. 1. A method for preventing or reducing the risk of developing a neurological disorder consequent to early-life seizure or hypoxic encephalopathy , comprising administering to a subject having had early-life seizure or hypoxic encephalopathy , an effective amount of an antagonist of CP-AMPAR , wherein CP-AMPAR lacks a GluA2 subunit.2. The method of claim 1 , wherein the antagonist is IEM14603. The method of claim 1 , wherein the antagonist is systemically administrable.4. A method for treating a subject suffering from enhanced CP-AMPAR function or expression claim 1 , said method comprising administering an effective amount of an antagonist of CP-AMPAR claim 1 , wherein CP-AMPAR lacks a GluA2 subunit to the subject.5. The method of claim 4 , wherein the subject is at a developmental stage having a predominance of GluA2-lacking AMPARs.6. The method of claim 4 , wherein the subject has an early-life seizure.7. The method of claim 4 , wherein the subject has hypoxic encephalopathy.8. The method of claim 4 , wherein the subject has a CDKL5 disorder claim 4 ,9. The method of claim 4 , wherein the subject further has one or more neurologic disorder.10. The method of claim 9 , wherein the one or more neurologic disorder is infantile spasms claim 9 , Lennox Gastaut syndrome claim 9 , Rett Syndrome claim 9 , West Syndrome claim 9 , and autism.11. The method of claim 4 , wherein the subject has epilepsy.12. The method of claim 4 , wherein the subject has an autism spectrum disorder.13. The method of claim 4 , wherein the subject has dementia.14. The method of claim 4 , wherein the subject has a neurodevelopmental delay disorder.15. The method of claim 4 , wherein the subject has a traumatic brain injury.16. The ...

SYNERGISTIC COMPOSITIONS COMPRISING (R)-2-(2-OXOPYRROLIDIN-1-YL)BUTANAMIDE AND (S)-2-(2-e OXOPYRROLEDIN-1-YL)BUTANAMEDE IN A NON-RACEMIC RATIO

The present invention relates to a composition of the enantiomers of 2-(2-oxopyrrolidin-1-yl)butanamide and pharmaceutically acceptable solvates or co-crystals thereof in a certain ratio, a pharmaceutical composition comprising said composition, its use as a medicament and the use of the inventive compositions or pharmaceutical compositions in the treatment and/or prevention of a disease or disorder typically and preferably selected from seizure-related disorders, peripheral sensory neuropathy, preferably peripheral neuropathic pain; seizure; depression; or cognitive impairment. 2. The composition of claim 1 , wherein the enantiomeric excess (ee) of said compound of formula (I) is equal to or higher than 20% and lower than or equal to 50%.3. The composition of claim 1 , wherein the enantiomeric excess (ee) of said compound of formula (I) is equal to or higher than 20% and lower than or equal to 40%.4. The composition of claim 1 , wherein the compound of formula (I) and/or pharmaceutically acceptable solvates or co-crystals thereof and compound of formula (II) and/or pharmaceutically acceptable solvates or co-crystals thereof are packaged separately.5. The composition of claim 1 , wherein the composition is a non-racemic mixture of 2-(2-oxopyrrolidin-1-yl)butanamide and pharmaceutically acceptable solvates or co-crystals thereof claim 1 , wherein the non-racemic mixture comprises the compound of formula (I) to the compound of formula (II) in an enantiomeric excess (ee) of the compound of formula (I) of equal to or higher than 20% and lower than or equal to 67%.6. A pharmaceutical composition comprising the composition of and a pharmaceutically acceptable carrier.7. A kit of parts comprising a compound of formula (I) and a compound of formula (II) and instructions for combining the compound of formula (I) and the compound of formula (II) to obtain an enantiomeric excess (ee) of the compound of formula (I) of equal to or higher than 20% and lower than or equal to 67%.8 ...

COMPOSITIONS AND METHODS FOR BLOCKING SODIUM CHANNELS

The disclosure provides methods for treating a subject suffering from a disease associated with sodium channel activity. The method comprises administering to the subject a therapeutically effective amount of a compound according to Formula II or Formula III described in the specification, or a pharmaceutically acceptable salt, prodrug, tautomer, stereoisomer, hydrate, or solvate thereof. 117.-. (canceled)20. The pharmaceutical composition of claim 19 , wherein R13 is optionally substituted C-Calkyl.21. The pharmaceutical composition of claim 20 , wherein R13 is CH.29. The compound of claim 28 , wherein R13 is optionally substituted C1-C6 alkyl.30. The compound of claim 29 , wherein R13 is CH.35. (canceled)36. (canceled) This application claims the benefit of priority to U.S. Provisional Patent Application No. 62/449,812 filed on Jan. 24, 2017, the disclosure of which is incorporated herein in its entirety by reference.Epilepsy, a neurological disorder, is characterized by recurrent spontaneous seizures within the brain and is a major public health issue affecting over 2 million Americans. In the United States, 1 in 26 people will develop epilepsy in their lifetime. Current treatments for epilepsy involve the suppression of seizure's using antiepileptic drugs (AEDs). Unfortunately, substantial proportions of patients (˜30%) continue to experience seizures even in the presence of optimal doses of AEDs and are considered pharmaco-resistant. Furthermore, many patients that achieve seizure control with medications suffer from medication induced neurotoxicity, sedation, and cognitive side effects (see, for example, Rivara M et al (2008) Bioorg Med Chem 18, 5460-62; Fantini M et al (2009) Bioorg Med Chem 17, 3642-48; Zuliani V et al (2010) Bioorg Med Chem 18, 7957-65; Rivara M et al (2012) Bioorg Med Chem Lett 22, 6401-04). In view of this, there is a continued need for the development of more effective and safer AEDs.There is a long felt need in the art for compositions ...

Use of Thiol Compounds to Treat Neurological Disease

The present disclosure relates, in general, to use of small diffusible thiols in the treatment of neurodegenerative diseases associated with glutamate excitotoxicity, protein aggregation and oxidative stress in the central nervous system, particularly in the brain. 1. A method of treating a neurological disease or disorder , an excitotoxicity disorder , a neurological disease or disorder characterized by aggregation of TDP-43 , or a neurological disease or disorder characterized by aggregation of superoxide dismutase 1 (SOD1) protein comprising administering a small thiol compound having a molecular weight <500 daltons , a log P >0.8 , and a TPSA <90 that can be oxidized by reactive-oxygen species after crossing the blood-brain barrier to a sulfinic or sulfonic acid and wherein the oxidized compound possesses GABAergic , calcium channel inhibiting , glutamatergic or other neurologic activity.24.-. (canceled)5. The method of claim 1 , further characterized by aggregation of tau protein.6. The method of claim 1 , wherein the disease or disorder is amyotrophic lateral sclerosis (ALS) claim 1 , frontotemporal lobar degeneration claim 1 , traumatic brain injury claim 1 , chronic traumatic encephalopathy (CTE) claim 1 , Alzheimer's disease claim 1 , ischemia or epilepsy.7. The method of wherein the disease is familial or sporadic ALS.8. A method of preventing or ameliorating brain injury caused by trauma comprising administering to a subject in need thereof a small thiol compound having a molecular weight <500 daltons claim 6 , a log P >0.8 claim 6 , and a TPSA <90 that can be oxidized by reactive-oxygen species after crossing the blood-brain barrier to a sulfinic or sulfonic acid and where the oxidized compound possesses GABAergic claim 6 , calcium channel inhibiting claim 6 , glutamatergic or other neurologic activity.9. (canceled)10. The method of claim 1 , wherein the compound reduces protein aggregation claim 1 , neuronal overexcitation or oxidative stress ...

ISOFORM-SPECIFIC CALPAIN INHIBITORS, METHODS OF IDENTIFICATION, AND USES THEREOF

Molecules that selectively inhibit or stimulate the activity of isoforms of calpains are presented. Methods for screening and characterizing such molecules are also presented. Specific functions of calpain-1 calpain-2 in long term potentiation (LTP), learning and memory, neurodegeneration and diseases of synaptic dysfunction are characterized using novel calpain inhibitors, substrates and related methods. The compounds, compositions, and methods described herein are expected to be useful, for treating neurodegenerative diseases and other diseases of synaptic function, and for modulating cognition in patients in need thereof. 5. A composition comprising a molecule according to claim 1 , wherein its calpain-2 inhibition constant (Ki) is equal to claim 1 , or more claim 1 , than 10-fold lower than its Ki for calpain-1.6. A composition according to claim 5 , wherein the molecule inhibits neuronal cell death claim 5 , enhances memory.7. (canceled)8. A method of treating glaucoma or a neurological disease claim 5 , comprising administering a composition according to .9. (canceled)10. A composition comprising a pharmaceutically acceptable excipient and a synthetic polypeptide having at least 95% identity to the entirety of any one of SEQ ID NO: 1-68 claim 5 , 74-193 claim 5 , or 201-222 claim 5 , wherein the synthetic polypeptide has a calpain-2 inhibition constant (Ki) that is equal to claim 5 , or more claim 5 , than 10-fold lower than its Ki for calpain-1.11. A composition according to claim 10 , wherein the synthetic polypeptide additionally comprises a membrane transduction synthetic polypeptide.1215-. (canceled)16. A composition according to claim 10 , wherein the molecule inhibits neuronal cell death claim 10 , or enhances memory.17. (canceled)18. A method of treating glaucoma claim 10 , or treating a neurological disease claim 10 , comprising administering a composition according to .19. (canceled)20. A composition according to claim 11 , wherein the molecule ...

METHOD FOR TREATING EPILEPSY

In certain embodiments, the present disclosure is directed to methods and uses for treating a mammal having an epileptic seizure disorder or being at risk for having an epileptic seizure disorder, comprising administering certain herein disclosed isolated fenfluramine enantiomers that are surprisingly effective as anti-epilepsy drugs (AEDs), despite having lower anti-seizure potency than fenfluramine racemate, by virtue of also being less cardiotoxic than fenfluramine racemate. Preferred embodiments contemplate treatment of Dravet syndrome; other preferred embodiments contemplate treatment of other epileptic seizure disorders. 1. A method of treating epilepsy or an epileptic seizure disorder , comprising administering to a human subject in need thereof a therapeutically effective amount of (R)-fenfluramine or a pharmaceutically acceptable salt thereof;wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an enantiomeric excess (ee) greater than 80%.2. The method of claim 1 , wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an ee greater than 90%.3. The method of claim 1 , wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an ee greater than 95%.4. The method of claim 1 , wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an ee greater than 97%.5. The method of claim 1 , wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an ee greater than 99%.6. The method of claim 1 , wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an ee between 80% and 99%.7. The method of claim 1 , wherein the (R)-fenfluramine or pharmaceutically acceptable salt thereof has an ee between 90% and 99%.8. The method of claim 1 , wherein the subject suffers from Dravet syndrome.9. A pharmaceutical composition comprising (R)-fenfluramine or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients;wherein ...

Mitigation of cns disorders by combination therapy using neurosteroids, and ampa blockers

Provided are compositions and methods for treating epilepsy, including epilepsy caused by exposure to organophosphate nerve agents, that entail co-formulation and/or co-administration of a benzodiazepine, a neurosteroid and an AMPA receptor antagonist.

SYNTHETIC TRANSDERMAL CANNABIDIOL FOR THE TREATMENT OF FOCAL EPILEPSY IN ADULTS

The present technology relates to a method of reducing seizure frequency in a subject having epilepsy by transdermally administering an effective amount of cannabidiol (CBD) to the subject wherein the seizure frequency is reduced. 1. A method of reducing seizure frequency in a subject having epilepsy , the method comprising:transdermally administering an effective amount of cannabidiol (CBD) to the subject wherein the seizure frequency is reduced.228-. (canceled) This application claims the benefit of and priority to U.S. Provisional Patent Application Nos. 62/560,446 filed Sep. 19, 2017; 62/593,575 filed Dec. 1, 2017; 62/613,160 filed Jan. 3, 2018; 62/652,995 filed Apr. 5, 2018; and 62/660,198 filed Apr. 19, 2018. The entire contents of each of which are incorporated herein by reference in their entirety.The present disclosure relates to a method of reducing seizure frequency in a subject having epilepsy by transdermally administering an effective amount of cannabidiol (CBD) to the subject wherein the seizure frequency is reduced.Cannabinoids are a class of chemical compounds found in the Cannabis plant. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and Δ9-tetrahydrocannabinol, or THC. CBD lacks the psychoactive effects of THC. Studies have shown that CBD can be used to treat disorders such as epilepsy, arthritis, and cancer.Epilepsy is a disease characterized by an enduring predisposition to generate seizures and by the neurobiological, cognitive, psychological and social consequences of the condition. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. The seizures in epilepsy may be related to a genetic disorder or a brain injury such as trauma or stroke, but most often the cause is unknown. There are more than 200,000 cases of epilepsy in the United States per year.Generalized epilepsy affects both hemispheres of the brain from onset. Focal ...

METHOD FOR TREATING SEIZURES

Methods for treating seizures, more particularly treating seizures associated with epilepsy. 1. A method for treating seizures in a subject in need thereof , comprising administering to the subject a therapeutically effective amount of an agent that inhibits the CD40-CD40L interaction and pathway in the brain.2. The method of claim 1 , wherein the subject has increased susceptibility for epilepsy.3. The method of claim 2 , wherein the increased susceptibility for epilepsy is due to a condition selected from the group consisting of traumatic brain injury claim 2 , brain tumors claim 2 , stroke claim 2 , neuroinflammation claim 2 , dementia claim 2 , drug intoxication claim 2 , chemical intoxications claim 2 , neurodevelopmental disorders claim 2 , and metabolic disorders of the nervous system.4. The method of claim 2 , wherein the increased susceptibility for epilepsy is due to a systemic disease selected from the group consisting of diabetes claim 2 , hypertension claim 2 , chronic inflammatory disorders claim 2 , and immunological disorders.5. The method of claim 1 , wherein the subject manifests epilepsy.6. The method of claim 5 , wherein the epilepsy is Temporal Lobe Epilepsy (TLE).7. The method of claim 5 , wherein the epilepsy is status epilepticus.8. The method of claim 1 , wherein the subject does not manifest epilepsy.9. The method of claim 1 , wherein the agent is an antagonist of CD40 or CD40L.10. The method of claim 9 , wherein the antagonist is a CD40L antagonist.11. The method of claim 10 , wherein the CD40L antagonist is an anti-CD40L antibody.12. The method of claim 11 , wherein the anti-CD40L antibody comprises a fully humanized anti-CD40L antibody.13. The method of claim 11 , wherein the anti-CD40L antibody comprises a fragment of a fully functional anti-CD40L antibody.14. The method of claim 11 , wherein the anti-CD40L antibody is PEGylated.15. The method of claim 11 , wherein the anti-CD40L antibody is administered in a pharmaceutically acceptable ...

Treatment of epileptic disorders in feline animals

A method for treatment and/or prevention of one or more epileptic disorders in a feline animal, preferably a cat, includes administration of 1-(4-chlorophenyl)-4-(4-morpholinyl)-2.5-dihydro-1H-imidazol-2-one or a physiologically acceptable salt thereof to the feline animal.

A19-144, A2-73 and Certain Anticholinesterase Inhibitor Compositions and Method for Anti-Seizure Therapy

This invention concerns a dosage form comprising a therapeutically effective amount of A19-144 or A2-73 and a therapeutically effective amount of at least one AED. This invention further encompasses a method of treating a subject in need of such treatment comprising administering a therapeutically effective amount of A19-144 or A2-73 in conjunction with an therapeutically effective amount of an AED. 1. A method of treating seizures in a subject in need of such treatment comprising administering an therapeutically effective amount of A19-144 or a combination of A19-144 and A2-73 in conjunction with a sub-MED amount of an AED.2. The method of wherein said administering of A19-144 or the combination of A19-144 and A2-73 in conjunction with a sub-MED amount of an AED is co-timely.3. The method of wherein said administering of A19-144 or the combination of A19-144 and A2-73 in conjunction with a sub-MED amount of an AED is coordinated.4. The method of wherein the at least one AED is selected from the group consisting of donepezil claim 1 , memantine claim 1 , galantamine claim 1 , and rivastigmine claim 1 , wherein the sub-MED dose of donepezil is 0.5 mg or less claim 1 , the sub-MED dose of memantine is 0.5 mg or less claim 1 , the sub-MED dose of galantamine is 6 mg or less; and the sub-MED dose of rivastigmine is about 0.5 mg.5. The method of wherein the sub-MED dose and the at least one AED are selected from the group consisting of:less than about 8 mg/day of acetazolamide;less than about 1.5 mg/day for of Clonazepam for an adult, less than about 0.01 mg/kg/day of Clonezepam for a child up to 10 years of age or 30 kg of body weight;less than about 30 (mg) of Clorazepate;less than about 0.1 mg/kg of Lorazepam;less than about 0.2 mg/kg of Midazolam;less than about 7.5 mg/day of Carbamazepine;less than about 0.2 mg/kg of Diazepam;less than about 30 mg/day of Chlordiazepoxide;less than about 5 mg/day for body weight 30 kg or less, and less than about 10 mg/day for body ...

A19-144, A2-73 and Certain Anticholinesterase Inhibitor Compositions and Method for Anti-Seizure Therapy

This invention concerns a dosage form comprising a therapeutically effective amount of A19-144 or A2-73 and a therapeutically effective amount of at least one AED. This invention further encompasses a method of treating a subject in need of such treatment comprising administering a therapeutically effective amount of A19-144 or A2-73 in conjunction with any therapeutically effective amount of an AED. 1. A dosage form comprising a therapeutically effective amount of an active , (i) tetrahydro-N-methyl-2,2-diphenyl-3-furanomethanamine, or a pharmaceutically acceptable salt thereof;', '(ii) tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanomethanamine, or a pharmaceutically acceptable salt thereof; or a combination of (i) and (ii); and, 'wherein the active is'}wherein the therapeutically effective amount is the amount to elicit pharmacological response of reduction in the number of seizures.2. The dosage form of claim 1 , wherein the therapeutically effective amount is 0.5-10 mg/day.3. The dosage form of claim 1 , wherein the dosage form further comprises a pharmaceutical excipient suitable for oral or parenteral administration.4. The dosage form of claim 1 , further comprising a sub-MED amount of at least one anti-epilepsy drug (AED).5. The dosage form of claim 4 , wherein the sub-MED amount of the at least one anti-epilepsy drug (AED) is selected from the group consisting ofless than 5 mg/day of donepezil;less than 0.5 mg/day of memantine;less than 8 mg/day of galantamine;less than 3 mg/day of rivastigmine;less than about 8/day mg of acetazolamide;less than about 1.5 mg/day of Clonazepam for an adult, less than about 0.01 mg/kg/day of Clonazepam for a child up to 10 years of age or 30 kg of body weight;less than about 30 mg/day of Clorazepate;less than about 0.1 mg/kg/day of Lorazepam;less than about 0.2 mg/kg/day of Midazolam;less than about 7.5 mg/day of Carbamazepine;less than about 0.2 mg/kg/day of Diazepam;less than about 30 mg/day of Chlordiazepoxide;less than about ...

Prodrugs of modulators of the nmda receptor

The present invention is directed to novel prodrugs of modulators of the NMDA receptor. Separate aspects of the inventions are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat neurological disorders or neuropsychiatric disorders such as depression.

Methods and compositions for the treatment of seizure-related disorders

Compositions and methods are provided for administering a pharmaceutical composition to a human patient. Compositions are administered to a human patient orally, once daily, at a therapeutically effective dose. The pharmaceutical compositions comprise a drug selected from the group consisting of brivaracetam, divalproex, lacosamide, levetiracetam, oxcarbazepine, vigabatrin, and pharmaceutically acceptable salts of any of the foregoing, and at least one excipient. At least one of said at least one excipients modifies the release of said drug to provide an extended release form. The pharmaceutical composition have pharmacokinetic properties recited in the claims.

USE OF CANNABINOIDS IN THE TREATMENT OF EPILEPSY

The present invention relates to the use of a therapeutically effective amount of cannabidiolic acid (CBDA) in the treatment of epilepsy. In one embodiment the CBDA is used in the treatment of generalised seizures, preferably tonic-clonic seizures.

Methods for enhancing the bioavailability and exposure of a voltage-gated potassium channel opener

In certain embodiments, the present disclosure is directed to methods and uses for treating seizure disorders in a human, wherein the methods and uses comprise orally administering a therapeutically effective amount of the voltage-gated potassium channel allosteric modulator, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (Compound A), to the human in need thereof, for example, under fed conditions. The present disclosure is further directed to various improved methods of therapy and administration of Compound A.

ORAL VETERINARY COMPOSITION WITH GABAPENTIN

The present invention relates to a solid veterinary pharmaceutical composition, of oral administration comprising: a) a drug selected from gabapentin and/or fluoxetine or a pharmaceutically acceptable salt thereof, preferably gabapentin or an acceptable salt thereof in a concentration from 10 to 1000 mg; b) from 10% to 80% of the composition total weight of at least one silicon salt selected preferably from silicon dioxide, colloidal silicon dioxide, calcium silicate, magnesium silicate or combinations thereof; c) from 1% to 20% of the composition total weight of at least one polyoxyethylenated sorbitan ester, preferably selected from sorbitan monolaurate, sorbitan monooleate and sorbitan trioleate, or combinations thereof; and d) one or more pharmaceutically acceptable excipients; such that it is optimally prepared as a veterinary pharmaceutical product that exhibits safety and efficacy in mammalian animals, preferably in companion animals. 1. A solid veterinary pharmaceutical composition for oral administration 5 comprising: a) a drug selected from gabapentin and/or fluoxetine or a pharmaceutically acceptable salt thereof in a concentration of 1 to 1000 mg; b) from 10% to 80% of the composition total weight of at least one silicon salt selected preferably from silicon dioxide , colloidal silicon dioxide , calcium silicate , magnesium silicate or combinations thereof; c) from 1% to 20% of the composition total weight of at least one polyoxyethylenated sorbitan ester , preferably selected from sorbitan monolaurate , sorbitan monooleate and sorbitan trioleate or combinations thereof and d) one or more pharmaceutically acceptable excipients2. A solid veterinary pharmaceutical composition for oral administration according to claim 1 , characterized in that it comprises gabapentin or a pharmaceutically acceptable salt thereof in a concentration of 100 to 400 mg.3. A solid veterinary pharmaceutical composition for oral administration according to claim 1 , characterized ...

Cannabidiol preparations and its uses

Cannabidiol (CBD) is a cannabinoid designated chemically as 2-[(1R,6R)-3-Methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol. Its empirical formula is C21H30O2 and its molecular weight is 314.46. CBD is a cannabinoid that naturally occurs in the Cannabis sativa L. plant. CBD is a white to pale yellow crystalline solid which is insoluble in water and soluble in organic solvents. The present invention encompasses the surprising recognition that certain CBD preparations which are prepared from a botanical origin are more effective in treating diseases or disorders than preparations of CBD which are synthetic or purified to the extent no other impurities in the form of other cannabinoids are present. Prior CBD compositions have been prepared such that no psychoactive components, e.g., tetrahydrocannabinol (THC), remain in the final CBD preparation. Surprisingly, the absence of such minor impurities reduces the efficacy of CBD treatment. Such CBD preparations are characterized by chemical components and/or functional properties that distinguish them from prior CBD compositions. One or more components of the preparations described herein provide an unexpectedly synergistic effect when utilized in combination.

Use of i-brd9 or derivatives thereof in preparing anti-epileptic drugs

Provided are methods of using bromodomain-containing protein 9 inhibitor (I-BRD9) or a derivative thereof in preparation of anti-epileptic drugs. The I-BRD9 has significant effects on anticonvulsion, prolonging of convulsion latency, and reduction of seizure level, and can be used for preparing anti-epileptic drug preparations.

Modified release preparations containing oxcarbazepine and derivatives thereof

Controlled-release preparations of oxcarbazepine and derivatives thereof for once-a-day administration are disclosed. The inventive compositions comprise solubility- and/or release enhancing agents to provide tailored drug release profiles, preferably sigmoidal release profiles. Methods of treatment comprising the inventive compositions are also disclosed.

Long term drug delivery devices with polyurethane based polymers and their manufacture

This invention is related to the use of polyurethane based polymer as a drug delivery device to deliver biologically active compounds at a constant rate for an extended period of time and methods of manufactures thereof. The device is very biocompatible and biostable, and is useful as an implant in patients (humans and animals) for the delivery of appropriate bioactive substances to tissues or organs. The drug delivery device for releasing one or more drugs at controlled rates for an extended period of time to produce local or systemic pharmacological effects comprises: 1. a reservoir, said reservoir comprising; 2. at least one active ingredient; and, optionally, 3. at least one pharmaceutically acceptable carrier; a polyurethane based polymer completely surrounding the reservoir.

Detection of an autoantibody

A diagnostically useful carrier includes a peptide including the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or a variant thereof. A kit, a composition, a detection method, use for detecting a neurological disease, a human autoantibody specifically binding to Drebrin and a therapeutic compound or combination for use in the treatment of a neurological use are also useful.

USE OF DESIGNER RECEPTORS EXCLUSIVELY ACTIVATED BY DESIGNER DRUGS AND ULTRASOUND IN THE TREATMENT OF SEIZURE DISORDERS

Methods and compositions for treating a seizure disorder are provided which include administering to the patient a vector encoding a modified receptor for delivery of the modified receptor to the target location, the modified receptor being modified to be activated by a synthetic ligand, wherein the modified receptor inhibits neuronal firing when activated; and administering to the patient the synthetic ligand. Also provided are methods and compositions for treating a seizure disorder in a patient in need thereof by administering to the patient a vector encoding a modified receptor for delivery of the modified receptor to the target location, the modified receptor being modified to be activated by a synthetic ligand, wherein the modified receptor increases neuronal firing when activated; and administering to the patient the synthetic ligand. The methods are used to improve or alleviate one or more symptoms of a seizure disorder. 1. A method of treating a seizure disorder in a patient in need thereof comprising:administering to the patient an adeno-associated virus vector encoding hM4Di for delivery of hM4Di to a target location, the vector including a human CaMK2A promoter, a woodchuck hepatitis virus post-transcriptional regulatory element, and a bovine growth hormone polyadenylation sequence; andadministering to the patient a synthetic ligand which activates hM4Di.2. The method of treating a seizure disorder according to claim 1 , wherein the vector includes two inverted terminal repeats claim 1 , a SV40 origin of replication claim 1 , a pUC19 origin of replication claim 1 , and an ampicillin resistance gene.3. The method of treating a seizure disorder according to claim 2 , wherein the vector is pAM/hCaMK2A-hM4D(Gi)-WPRE-BGHpA.4. The method of treating a seizure disorder according to claim 1 , wherein the vector includes a fluorescence reporter gene.5. The method of treating a seizure disorder according to claim 1 , wherein the adeno-associated virus vector is ...

METHODS OF TREATING EPILEPSY, SEIZURE DISORDERS AND SUDDEN UNEXPECTED DEATH IN EPILEPSY

The present system is directed in several embodiments to a method of administration of a therapeutic composition for treatment of seizures resulting from epilepsy and other seizure disorders. The method includes administering one or more therapeutic compositions comprising an effective amount of insulin directly to the subject patient's CNS, with no to minimal systemic exposure. Preferably, this method comprises administration of an effective amount of insulin to the upper third of a patient's nasal cavity, thereby bypassing the patient's blood-brain barrier and delivering the therapeutic composition directly to the patient's central nervous system. 1. A method for preventing and/or treating seizures in a patient , comprising:administering at least an effective amount of insulin to the upper third of the nasal cavity of the patient;enabling at least an effective amount of insulin to directly access the patient's central nervous system by bypassing the blood-brain barrier; andpreventing and/or treating the patient's seizures.2. The method of claim 1 , further comprising administering the insulin to a tissue innervated by the olfactory nerve and/or the trigeminal nerve claim 1 , wherein the administered insulin bypasses the blood-brain barrier to access the patient's central nervous system to treat the patient's seizures.3. The method of claim 1 , further comprising administering the at least an effective amount of insulin to the patient while the patient is experiencing a seizure.4. The method of claim 1 , further comprising administering the at least an effective amount of insulin to the patient after conclusion of a seizure.5. The method of claim 4 , further comprising administering the at least an effective amount of insulin to the patient while the patient is experiencing a seizure.6. The method of claim 1 , wherein the at least an effective amount of insulin is in the range of 1×10to 0.1 mg/kg.7. The method of claim 6 , wherein a more preferred dosage range for ...

Use of Thiol Compounds to Treat Neurological Disease

The present disclosure relates, in general, to use of small diffusible thiols in the treatment of neurodegenerative diseases associated with glutamate excitotoxicity, protein aggregation and oxidative stress in the central nervous system, particularly in the brain. 24.-. (canceled)5. The method of claim 1 , further characterized by aggregation of tau protein.6. The method of claim 1 , wherein the disease or disorder is amyotrophic lateral sclerosis (ALS) claim 1 , frontotemporal lobar degeneration claim 1 , traumatic brain injury claim 1 , chronic traumatic encephalopathy (CTE) claim 1 , Alzheimer's disease claim 1 , ischemia or epilepsy.7. The method of wherein the disease is familial or sporadic ALS.9. (canceled)10. The method of claim 1 , wherein the compound reduces protein aggregation claim 1 , neuronal overexcitation or oxidative stress characteristic of neurodegenerative disorders.12. The method of claim 1 , wherein the administration reduces neuronal glutamate toxicity.13. (canceled)1528.-. (canceled)29. The method of claim 1 , wherein the administration improves one or more symptoms of diminished motor function claim 1 , mobility claim 1 , cognitive ability claim 1 , or other symptoms of an excitotoxicity disorder.30. The method of claim 29 , wherein one or more symptoms include diminished motor function claim 29 , mobility claim 29 , cognitive ability claim 29 , or other symptoms of an excitotoxicity disorder.31. The method of claim 1 , wherein the compound exhibits neuroprotective effects in a neuronal tissue-culture model of excitotoxicity claim 1 , oxidative stress claim 1 , glutamate overstimulation claim 1 , elevated intracellular calcium claim 1 , GABA receptor function claim 1 , mitochondrial stress or the consequences of these phenomena.32. The method of claim 1 , wherein the compound or its oxidized equivalent improves cell-viability claim 1 , reduces calcium transport claim 1 , relieves mitochondrial stress claim 1 , enhances mitophagy claim 1 , ...

USE OF CANNABINOIDS IN THE TREATMENT OF EPILEPSY

The present disclosure relates to the use of cannabidiol (CBD) for the treatment of atonic seizures. In particular the CBD appears particularly effective in reducing atonic seizures in patients suffering with etiologies that include: Lennox-Gastaut Syndrome; Tuberous Sclerosis Complex; Dravet Syndrome; Doose Syndrome; Aicardi syndrome; CDKL5 and Dup15q in comparison to other seizure types. The disclosure further relates to the use of CBD in combination with one or more anti-epileptic drugs (AEDs). 1. A method of treating seizures in a patient in need thereof , comprising administering to the patient cannabidiol (CBD) drug substance having a purity of at least 95% (w/w) CBD , wherein the patient is administered a starting dose of CBD of 5 mg/kg/day , and about 3 or about 4 days after administering the starting dose , the starting dose is increased by about 1-5 mg/kg.2. The method of claim 1 , wherein the starting dose is increased 4 days after administering the starting dose.3. The method of claim 1 , wherein the starting dose is increased by about 5 mg/kg.4. The method of claim 1 , wherein the dose of the CBD is increased to about 10 mg/kg/day.5. The method of claim 4 , wherein the dose of the CBD is further increased to about 20 mg/kg/day.6. The method of claim 4 , wherein the dose of CBD is further increased to about 25 mg/kg/day.7. The method of claim 1 , wherein the patient has Lennox-Gastaut Syndrome claim 1 , Dravet Syndrome claim 1 , tuberous sclerosis complex (TSC) claim 1 , Doose Syndrome claim 1 , Aicardi syndrome claim 1 , Myoclonic absence epilepsy claim 1 , febrile infection related epilepsy syndrome (FIRES) claim 1 , Sturge Weber claim 1 , CDKL5 or Dup15.8. The method of claim 1 , wherein the patient has Lennox-Gastaut Syndrome.9. The method of claim 1 , wherein the patient has Dravet Syndrome.10. The method of claim 1 , wherein the patient has TSC.11. The method of claim 1 , wherein the seizures are convulsive seizures.12. The method of claim 1 , ...

SOLID DOSAGE FORMS OF VIGABATRIN

The invention pertains to a solid dosage form comprising vigabatrin; a superdisintegrant, advantageously chosen from the list consisting of crospovidone, a cellulose derivative and a starch derivative; a non-reducing sugar, advantageously chosen from the list consisting of mannitol, xylitol, and sorbitol; and a stearate derivative, advantageously a stearate or stearyl fumarate salt, more advantageously sodium stearyl fumarate or magnesium stearate. 1. Solid dosage form comprising:vigabatrin;a superdisintegrant, advantageously chosen from the list consisting of crospovidone, a cellulose derivative and a starch derivative;a non-reducing sugar, advantageously chosen from the list consisting of mannitol, xylitol, and sorbitol; anda stearate derivative, advantageously a stearate or stearyl fumarate salt, more advantageously sodium stearyl fumarate or magnesium stearate.2. Solid dosage form according to claim 1 , wherein it comprises:vigabratin;crospovidone;mannitol; andsodium stearyl fumarate or magnesium stearate.3. Solid dosage form according to claim 1 , wherein it consists of vigabatrin claim 1 , crospovidone claim 1 , mannitol and sodium stearyl fumarate.4. Solid dosage form according to claim 1 , wherein vigabatrin represents between 65 and 90% claim 1 , preferably between 70 and 85% claim 1 , more preferably between 75 and 80% claim 1 , yet preferably between 78 and 80% by weight of the solid dosage form.5. Solid dosage form according to claim 1 , wherein the superdisintegrant represents between 7 and 15% claim 1 , preferably between 8 and 12% claim 1 , more preferably between 9 and 10% by weight of the solid dosage form.6. Solid dosage form according to claim 1 , wherein the non-reducing sugar represents between 7 and 15% claim 1 , preferably between 8 and 12% claim 1 , more preferably between 9 and 10% by weight of the solid dosage form.7. Solid dosage form according to claim 1 , wherein the stearate derivative represents between 0.5 and 2% claim 1 , preferably ...

Methods of Treating Epilepsy via Phosphodiesterase 4 (PDE4) Inhibition

Provided are methods of treating epilepsy. The methods include administering to an individual having epilepsy a therapeutically effective amount of a phosphodiesterase 4 (PDE4) inhibitor. Also provided are methods of identifying an anti-epileptic agent. Such methods include contacting a PDE4 polypeptide with a candidate agent in a PDE4 activity assay, where inhibition of activity of the PDE4 polypeptide by the candidate agent identifies the candidate agent as an anti-epileptic agent. 1. A method of treating epilepsy , comprising administering to an individual having epilepsy a therapeutically effective amount of a phosphodiesterase 4 (PDE4) inhibitor.2. The method according to claim 1 , wherein the PDE4 inhibitor is a small molecule.3. The method according to claim 2 , wherein the PDE4 inhibitor is selected from the group consisting of: AN2728 claim 2 , drotaverine claim 2 , ibudilast claim 2 , irsogladine claim 2 , piclamilast claim 2 , roflumilast claim 2 , rolipram claim 2 , theophylline claim 2 , apremilast claim 2 , and any combination thereof.4. The method according to claim 2 , wherein the PDE4 inhibitor is AN2728.5. The method according to claim 1 , wherein the PDE4 inhibitor inhibits one or more of PDE4A claim 1 , PDE4B claim 1 , PDE4C claim 1 , or PDE4D.6. The method according to claim 1 , wherein the PDE4 inhibitor exhibits selectivity among PDE4A claim 1 , PDE4B claim 1 , PDE4C claim 1 , and PDE4D.7. The method according to claim 6 , wherein the PDE4 inhibitor is selective for PDE4B.8. The method according to any one of to claim 6 , wherein the administering is by oral claim 6 , parenteral claim 6 , intranasal claim 6 , intrathecal claim 6 , intracranial claim 6 , or transdermal administration.9. The method according to claim 1 , wherein the PDE4 inhibitor inhibits expression of PDE4.10. The method according to claim 9 , wherein the PDE4 inhibitor is a nucleic acid-based inhibitor comprising a region complementary to a portion of a messenger RNA (mRNA) ...

METHODS FOR CONTROLLING SEIZURES BY MANIPULATING THE LEVELS OF MICRORNA-211 (miR-211) IN THE BRAIN

Method for controlling for the appearance of seizures in the mammalian brain comprising modifying the abundance of a specific miRNA-miR-211, for uses in preventing seizures and providing a model system to examine the effect of a drug or a treatment to seizures. 1. A method of treating a human or a non-human mammal subject suffering from:brain injury, concussion, or disruption of the blood brain barrier '(i) introducing into the brain of said human or non-human subject an oligonucleotide with the nucleic acid sequence of miR-211', 'the method comprising the step of2. The method of claim 1 , wherein said introducing into the brain of said human or non-human subject an oligonucleotide is done by either:(a) administering a miR-211 oligonucleotide mimetic to the bloodstream of said human or non-human subject, or(b) administering a miR-211 oligonucleotide mimetic into—or to the proximity of—the brain of said human or non-human subject.3. The method of claim 1 , wherein said human or a non-human mammal subject is suffering from disruption of the blood brain barrier following physical trauma to the head.4. The method of claim 1 , wherein said human or a non-human mammal subject suffering from disruption of the blood brain barrier following neuro-inflammatory or a neuro-infectious Disease or following Acute Ischemic Stroke.5. The method of claim 2 , wherein said mimetic molecule is selected from a group consisting of RNA claim 2 , locked nucleic acid (LNA) claim 2 , 2-0-methyl-blocked claim 2 , Morpholino and phosphorothioate oligonucleotides.5. The method of claim 2 , wherein said oligonucleotide is selected from the group consisting of: SEQ ID No. 1 claim 2 , SEQ ID No. 2 claim 2 , SEQ ID No. 3 claim 2 , SEQ ID No. 4 claim 2 , SEQ ID No. 5 claim 2 , SEQ ID No. 6.6. The method of claim 2 , wherein said introducing into the brain of said human or non-human subject an oligonucleotide with the nucleic acid sequence of miR-211 is done by administering a miR-211 oligonucleotide ...

SYNTHENTIC TRANSDERMAL CANNABIDIOL FOR THE TREATMENT OF FOCAL EPILEPSY IN ADULTS

The present technology relates to a method of reducing seizure frequency in a subject having epilepsy by transdermally administering an effective amount of cannabidiol (CBD) to the subject wherein the seizure frequency is reduced. 1. A method of reducing seizure frequency in a subject having epilepsy , the method comprising:transdermally administering an effective amount of cannabidiol (CBD) to the subject wherein the seizure frequency is reduced.2. The method of claim 1 , wherein the seizure frequency is reduced by 30%.3. The method of claim 1 , wherein the seizure frequency is reduced by 50%.4. The method of claim 1 , wherein focal onset seizures in adults are reduced.5. The method of claim 1 , wherein focal aware seizures are reduced.6. The method of claim 1 , wherein focal impaired awareness seizures are reduced.7. The method of claim 1 , wherein focal compared awareness with generalized tonic-clonic seizures are reduced.8. The method of claim 1 , wherein the subject has a high seizure frequency.9. The method of claim 1 , wherein the epilepsy is drug resistant epilepsy.10. The method of claim 1 , administering at least one anti-epileptic drug selected from the group consisting of levetiracetam claim 1 , carbamazepine claim 1 , topiramate claim 1 , lamotrigine claim 1 , lacosamide claim 1 , clonazepam claim 1 , valproate claim 1 , clobazam claim 1 , phenytoin claim 1 , eslicarbaazepine claim 1 , and oxcarbazepine.11. The method of claim 1 , wherein the CBD is (−)-CBD.12. The method of claim 1 , wherein the effective amount of CBD is between about 195 mg and about 780 mg total daily.13. The method of claim 1 , wherein the effective amount of CBD is 195 mg in divided daily doses.14. The method of claim 1 , wherein the effective amount of CBD is 390 mg in divided daily doses.15. The method of claim 1 , wherein the effective amount of CBD is 585 mg in divided daily doses.16. The method of claim 1 , wherein the effective amount of CBD is 780 mg in divided daily doses. ...

USE OF CANNABINOIDS IN THE TREATMENT OF EPILEPSY

The present invention relates to the use of cannabidiol (CBD) in the treatment of Sturge Weber syndrome. CBD appears particularly effective in reducing all types of seizures and non-seizure symptoms in patients suffering with Sturge Weber syndrome. Preferably the CBD used is in the form of a highly purified extract of such that the CBD is present at greater than 98% of the total extract (w/w) and the other components of the extract are characterised. In particular the cannabinoid tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 0.15% (w/w) and the propyl analogue of CBD, cannabidivarin, (CBDV) is present in amounts of up to 1%. Alternatively, the CBD may be a synthetically produced CBD. 115-. (canceled)16. A method of treating Sturge Weber syndrome in a subject , comprising administering to the subject a therapeutically effective amount of cannabidiol (CBD).17. The method of claim 16 , wherein the treating comprises treating seizures in a subject having Sturge Weber syndrome.18. The method of claim 16 , wherein the treating comprises treating non-seizure symptoms in a subject having Sturge Weber syndrome.1918. The method of claim 16 , wherein the non-seizure symptoms are one or more of mood claim 16 , behaviour claim 16 , cognitive function and general quality of life.20. The method of claim 16 , wherein the CBD is administered in combination with one or more concomitant anti-epileptic drugs (AEDs).21cannabis. The method of claim 16 , wherein the CBD is a highly purified extract of which comprises at least 98% (w/w) CBD.22. The method of claim 16 , wherein the extract comprises less than 0.15% tetrahydrocannabinol (THC).23. The method of claim 16 , wherein the extract further comprises up to 1% cannabidivarin (CBDV).24. The method of claim 16 , wherein the extract further comprises between 0.1 and 1.0% CBDV.25. The method of claim 16 , wherein the CBD is present as a synthetic compound.26. The method of claim 20 , wherein the ...

METHODS OF TREATING EPILEPSY AND NEURODEVELOPMENTAL DISORDERS

The present invention is directed to, in part, methods of preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. In some embodiments, methods of treating a neurodevelopmental disorder (e.g., epilepsy) comprising administering to a subject in need thereof a compound disclosed herein (e.g., a compound of Formula (I), (I-a), or (I-b), e.g., eleclazine) are provided. 6. The method of any one of the preceding claims , wherein Q is a covalent bond.7. The method of any one of the preceding claims , wherein Cy is aryl (e.g. , phenyl).8. The method of any one of the preceding claims , wherein Ris —O—R(e.g. , —OCF).9. The method of any one of the preceding claims , wherein n is 1.10. The method of any one of the preceding claims , wherein m is 0.11. The method of any one of the preceding claims , wherein Ris —Calkylene-R(e.g. , —CH—R).12. The method of any one of the preceding claims , wherein Ris heteroaryl (e.g. , a nitrogen-containing heteroaryl , e.g. , pyrimidinyl).13. The method of any one of the preceding claims , wherein each Ris independently hydrogen.14. The method of any one of the preceding claims , wherein each Ris independently hydrogen.16. The method of any one of the preceding claims , wherein the compound of Formula (I-a) or (I-b) is selected from a compound disclosed herein.18. The method of any one of the preceding claims , wherein the neurodevelopmental disorder , pediatric epilepsy , or refractory epilepsy comprises Dravet syndrome or a genetic epilepsy.19. The method of any one of preceding claims , wherein the neurodevelopmental disorder , pediatric epilepsy , or refractory epilepsy is associated with a mutation in ALDH7A1 , ALG13 , ARHGEF9 , ARX , ASAH1 , CDKL5 , CHD2 , CHRNA2 , CHRNA4 , CHRNB2 , CLN8 , CNTNAP2 , CPA6 , CSTB , DEPDC5 , DNM1 , EEF1A2 , EPM2A , EPM2B , GABRA1 , GABRB3 , GABRG2 , GNAO1 , GOSR2 , GRIN1 , GRIN2A , GRIN2B , ...

COMPOSITIONS AND METHODS FOR SELECTIVE GENE REGULATION

Provided herein are engineered transcription factors for selective upregulation of SCN1a and uses thereof for treating diseases and disorders, such as, Dravet syndrome. Also provided are microRNA binding sites and uses thereof for selective expression in parvalbumin neurons.

COMBINATIONS COMPRISING POSITIVE ALLOSTERIC MODULATORS OR ORTHOSTERIC AGONISTS OF METABOTROPIC GLUTAMATERGIC RECEPTOR SUBTYPE 2 AND THEIR USE

The present invention relates to combinations comprising a positive allosteric modulator (“PAM”) of metabotropic glutamatergic receptor subtype 2 (“mGluR2”) or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A (“SV2A”) ligand. 121-. (canceled)23. The method of claim 22 , wherein the SV2A ligand and a free base of Compound 2a are administered.24. The method of claim 22 , wherein one or both of the SV2A and Compound 2a or the pharmaceutically acceptable salt thereof is in a non-effective dosage.25. The method of claim 22 , wherein the SV2A ligand is selected from the group consisting of levetiracetam claim 22 , brivaracetam claim 22 , and seletracetam.26. The method of claim 25 , wherein the SV2A ligand is levetiracetam or brivaracetam.27. The method of claim 26 , wherein the SV2A ligand is levetiracetam.28. The method of claim 26 , wherein the SV2A ligand is brivaracetam.29. The method of claim 22 , wherein the SV2A ligand and Compound 2a or the pharmaceutically acceptable salt thereof are administered in separate dosage forms.30. The method of claim 29 , wherein the separate dosage forms comprise:(i) a first dosage form comprising the SV2A ligand, and at least one pharmaceutically acceptable excipient; and(ii) a second dosage form comprising Compound 2a or the pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.31. The method of claim 30 , wherein the first dosage form and the second dosage form are administered sequentially or simultaneously.32. The method of claim 31 , wherein the first dosage form and the second dosage form are administered sequentially.33. The method of claim 31 , wherein the first dosage form and the second dosage form are administered simultaneously.34. The method of claim 22 , wherein the SV2A ligand and Compound 2 ...

Method of increasing time between convulsive seizures

A method of increasing an average time between seizures in a human patient diagnosed with Dravet syndrome, comprising administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of days until the patient exhibits an increase from baseline in average time between convulsive seizures of 6 hours, days weeks or more.

METHOD OF REDUCING SEIZURE TYPE EXPERIENCED BY A DRAVET PATIENT

A method of reducing a particular type of seizure in a human patient diagnosed with Dravet syndrome, by administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of days until the patient exhibits a reduction from baseline in seizures of a particular type. The reduction may be of one, two or three specific types of seizures. 1. A method of treating a patient diagnosed with Dravet syndrome , comprising:administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base or acid thereof; andrepeating the administering over a period of days until the patient exhibits a reduction from baseline in a seizure type experienced by the patient.2. The method as claimed in claim 1 , wherein the fenfluramine is the only active ingredient administered to the patient.3. The method of claim 1 , further comprising administering a co-therapeutic agent.4. The method as claimed in claim 1 , wherein two seizure types are reduced.5. The method as claimed in claim 1 , wherein three seizure types are reduced.6. The method as claimed in claim 1 , wherein the seizure type reduced is selected from the group consisting of non-convulsive seizures claim 1 , generalized seizures claim 1 , myoclonic seizures claim 1 , absence seizures claim 1 , and febrile seizures claim 1 , or any combination thereof.7. The method as claimed in claim 1 , further comprising:recording seizure types experienced daily by the patient in an electronic diary.8. The method of claim 3 , wherein the co-therapeutic agent is selected from the group consisting of claim 3 , carbamazepine claim 3 , ethosuximide claim 3 , fosphenytoin claim 3 , lamotrigine claim 3 , levetiracetam claim 3 , phenobarbital claim 3 , topiramate claim 3 , valproic acid claim 3 , valproate claim 3 , verapamil claim 3 , and benzodiazepines such as clobazam claim 3 , ...

METHOD OF REDUCTION MEDICATION IN TREATING DRAVET SYNDROME

A method of reducing dosing of a concomitant medication in a human patient diagnosed with Dravet syndrome, by administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of days while reducing the dose of one or more concomitant anti-seizure or anti-epileptic drugs (AEDs) from baseline and thereby decreasing the amount of medication given to the patient while reducing adverse side effects. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided. 1. A method of treating a patient diagnosed with Dravet syndrome , comprising:administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base or acid thereof;administering to the patient over a period of days a concomitant anti-epileptic drug (AED); andcontinuing to administer the fenfluramine and the AED over a period of days while gradually reducing AED administered while maintaining efficacy of treatment.2. The method as claimed in claim 1 , wherein the concomitant AED is reduced in increments while monitoring efficacy of the treatment.3. The method of claim 2 , wherein the incremental reduction continues over a period of days.4. The method of claim 2 , wherein the incremental reduction continues over a period of weeks.5. The method of claim 2 , wherein the incremental reduction continues over a period of months.6. The method of claim 3 , wherein the reduction continues until the patient no longer receives a dose of the concomitant AED.7. The method of claim 1 , wherein the AED is selected from the group consisting of claim 1 , carbamazepine claim 1 , ethosuximide claim 1 , fosphenytoin claim 1 , lamotrigine claim 1 , levetiracetam claim 1 , phenobarbital claim 1 , topiramate claim 1 , valproic acid claim 1 , valproate claim 1 , verapamil claim 1 , and benzodiazepines such as clobazam ...

METHOD OF TREATING SELECTED PATIENT POPULATION EXPERIENCING DRAVET SYNDROME

Provided herein is a method of treating a selected patient population, wherein the patient population is selected based on a determination that the patients have previously been non-responsive when treated with cannabidiol. In some embodiments, the method comprises selecting the patient based on a previously failed treatment with cannabidiol, based on lack of efficacy or tolerability. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided. The method comprises identifying a population of patients diagnosed with Dravet syndrome who were found previously to have been non-responsive when treated with cannabidiol. The selected population of patients is then treated by administering, to each identified patient, a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of a day or days, or over a period of weeks, months or years, until the patient exhibits a reduction from baseline in convulsive seizure frequency. 1. A method of treating a patient in a selected patient population diagnosed with Dravet syndrome , comprising:determining a patient has previously been non-responsive when treated with cannabidiol or the patient's response to cannabidiol diminished over time;identifying the patient so determined as being non-responsive;administering to the non-responsive patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base or acid thereof; andrepeating the administering over a period of days until the patient exhibits a reduction from baseline in convulsive seizure frequency.2. The method as claimed in claim 1 , wherein the fenfluramine is the only active ingredient administered to the patient.3. The method of claim 1 , further comprising:administering a co-therapeutic agent.4. The method of claim 3 , wherein the co-therapeutic agent is selected from the group consisting of ...

METHOD OF TREATING SELECTED PATIENT POPULATION EXPERIENCING DRAVET SYNDROME

Provided herein is a method of treating a selected patient population, wherein the patient population is selected based on a determination that the patients have previously been non-responsive when treated with stiripentol. In some embodiments, the method comprises selecting the patient based on a previously failed treatment with stiripentol, based on lack of efficacy or tolerability. Pharmaceutical compositions and formulations for use in practicing the subject methods are also provided. The method comprises identifying a population of patients diagnosed with Dravet syndrome who were found previously to have been non-responsive when treated with stiripentol. The selected population of patients is then treated by administering, to each identified patient, a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of a day or days, or over a period of weeks, months or years, until the patient exhibits a reduction from baseline in convulsive seizure frequency. 1. A method of treating a patient in a selected patient population diagnosed with Dravet syndrome , comprising:determining a patient has previously been non-responsive when treated with stiripentol or the patient's response to stiripentol diminished over time;identifying the patient so determined as being non-responsive;administering to the non-responsive patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base or acid thereof; andrepeating the administering over a period of days until the patient exhibits a reduction from baseline in convulsive seizure frequency.2. The method as claimed in claim 1 , wherein the fenfluramine is the only active ingredient administered to the patient.3. The method of claim 1 , further comprising:administering a co-therapeutic agent.4. The method of claim 3 , wherein the co-therapeutic agent is selected from the group consisting of ...

Ketogenic diet compatible fenfluramine formulation

A method of treating symptoms of a subtype of epilepsy, e.g., Dravet syndrome, in a patient diagnosed with a subtype of epilepsy, by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient. Also provided are compositions and kits finding use in practicing embodiments of the methods.

USE OF MIR101 OR MIR128 IN THE TREATMENT OF SEIZURE DISORDERS

Methods of treating a seizure disorder in a patient in need thereof are provided which include delivering to the patient an effective amount of a composition that increases the level of microRNA-101 molecules in brain cells of the patient. Methods of treating a seizure disorder in a patient in need thereof are provided which include delivering to the patient an effective amount of a composition that increases the level of microRNA-128 molecules in brain cells of the patient. Methods of treating a seizure disorder in a patient in need thereof are provided which include administering a vector encoding microRNA-101, pri-miR101 or pre-miR101 to the patient. Methods of treating a seizure disorder in a patient in need thereof are provided which include administering a vector encoding microRNA-128, pri-miR128 or pre-miR128 to the patient. In embodiments, increased levels of microRNA-101 and/or microRNA-128 cause improvement in one or more symptoms of the seizure disorder. 1. A method of treating a seizure disorder in a patient in need thereof comprising administering to the patient an effective amount of a pharmaceutical composition that increases the level of microRNA-101 molecules in the patient's brain ,2. The method according to claim 1 , wherein the composition includes microRNA-101 claim 1 , pri-miR101 or pre-miR101.3. The method according to claim 1 , wherein the composition includes a vector including nucleic acid encoding microRNA-101 claim 1 , pri-miR101 or pre-miR101.4. The method according to claim 3 , wherein after the administering claim 3 , microRNA-101 claim 3 , pri-miR101 or pre-miR101 is expressed claim 3 , and expression of microRNA-101 claim 3 , pri-miR101 or pre-miR101 claim 3 , in the patient is associated with reduced symptoms of the seizure disorder.5. The method according to claim 3 , wherein the nucleic acid encoding microRNA-101 claim 3 , pri-miR101 or pre-miR101 claim 3 , is operably linked to a promoter selected from the group consisting of CAG ...

Formulation of lacosamide

A modified release formulation of lacosamide.

PREGABALIN-CONTAINING, ORAL SUSTAINED-RELEASE TRIPLE LAYER TABLET

Disclosed a pregabalin-containing, high swellable, oral sustained-release triple layer tablet suitable for administration once daily. 1. A multilayer tablet comprising:an upper layer and a lower layer comprising a swellable polymer; andan intermediate layer comprising a medium transfer agent, the intermediate layer being positioned between the upper layer and the lower layer,wherein the tablet comprises pregabalin or a pharmaceutically acceptable salt thereof as an active ingredient.2. The multilayer tablet according to claim 1 , wherein the upper layer and the lower layer further comprise pregabalin or a pharmaceutically acceptable salt thereof claim 1 , and wherein the intermediate layer also further comprises pregabalin or a pharmaceutically acceptable salt thereof.3. The multilayer tablet according to claim 1 , wherein the medium transfer agent absorbs the aqueous medium and transfers it to the upper layer and the lower layer.4. The multilayer tablet according to claim 1 , wherein the medium transfer agent is an excipient having solubility that 10 mL or less of water is required to dissolve the medium transfer agent of 1 g.5. The multilayer tablet according to claim 1 , wherein the medium transfer agent is hydrophilic.6. The multilayer tablet according to claim 1 , wherein the medium transfer agent is one or more selected from the group consisting of sugars claim 1 , polyvinylpyrrolidone claim 1 , salts claim 1 , organic acids claim 1 , starch claim 1 , microcrystalline cellulose claim 1 , and low-substituted hydroxypropylcelluloses.7. The multilayer tablet according to claim 6 , wherein the medium transfer agent is one or more selected from the group consisting of dextrose claim 6 , dextrate claim 6 , dextrin claim 6 , lactose claim 6 , sucrose claim 6 , glucose claim 6 , mannitol claim 6 , isomalt claim 6 , xylitol claim 6 , erythritol claim 6 , sorbitol claim 6 , polyvinylpyrrolidone claim 6 , sodium chloride claim 6 , magnesium chloride claim 6 , sodium ...

CANNABIDIOL PREPARATIONS AND ITS USES

Cannabidiol (CBD) is a cannabinoid designated chemically as 2-[(IR,6R)-3-Methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol. Its empirical formula is CHOand its molecular weight is 314.46. CBD is a cannabinoid that naturally occurs in the L. plant. CBD is a white to pale yellow crystalline solid which is insoluble in water and soluble in organic solvents. The present invention encompasses the surprising recognition that certain CBD preparations which are prepared from a botanical origin are more effective in treating diseases or disorders than preparations of CBD which are synthetic or purified to the extent no other impurities in the form of other cannabinoids are present. Prior CBD compositions have been prepared such that no psychoactive components, e.g., tetrahydrocannabinol (THC), remain in the final CBD preparation. Surprisingly, the absence of such minor impurities reduces the efficacy of CBD treatment. Such CBD preparations are characterized by chemical components and/or functional properties that distinguish them from prior CBD compositions. One or more components of the preparations described herein provide an unexpectedly synergistic effect when utilized in combination. 1. A cannabidiol (CBD) preparation comprising greater than or equal to 90% (w/w) CBD based on total amount of cannabinoid in the preparation and the remainder comprises other cannabinoids , wherein the other cannabinoids comprise tetrahydrocannabinol (THC) wherein the THC is present as a mixture of trans-THC and cis-THC , and wherein the ratio of trans-THC to cis-THC is about 0.7:1.0 to about 5.0:1.0.2. The CBD preparation of claim 1 , comprising not more than 1.5% (w/w) THC based on total amount of cannabinoid in the preparation.3. The CBD preparation of claim 1 , comprising about 0.01% to about 0.1% (w/w) THC based on total amount of cannabinoid in the preparation.4. The CBD preparation of claim 1 , comprising about 0.02% to about 0.05% (w/w) THC based on total amount ...

TREATMENT OF CNS CONDITIONS

Aspects of the present invention relate to a method of treating an epileptic encephalopathy in a mammal in need thereof, comprising administering a composition comprising an effective amount of (4-benzyl-4-hydroxypiperidin-1-yl) (2,4′-bipyridin-3-yl)methanone or a pharmaceutically acceptable salt thereof to the mammal. 1. A method of treating an epileptic encephalopathy in a mammal in need thereof , comprising administering a composition comprising an effective amount of (4-benzyl-4-hydroxypiperidin-1-yl) (2 ,4′-bipyridin-3-yl)methanone or a pharmaceutically acceptable salt thereof to the mammal.2. The method of claim 1 , wherein the epileptic encephalopathy is selected from the group of Dravet syndrome claim 1 , Early myoclonic encephalopathy claim 1 , Epilepsy with continuous spike-and-waves during slow-wave sleep other than Landau-Kleffner syndrome claim 1 , epilepsy of infancy with migrating focal seizures claim 1 , Hypothalamic epilepsy claim 1 , Landau-Kleffner syndrome claim 1 , Lennox-Gastaut syndrome claim 1 , Doose syndrome claim 1 , Myoclonic status in non-progressive encephalopathies claim 1 , Ohtahara syndrome or early infantile epileptic encephalopathy claim 1 , West syndrome claim 1 , Glycine encephalopathy claim 1 , 15q duplication syndrome and Tuberous Sclerosis Complex and seizures associated with mutations in CHD2 claim 1 , Cyclin-Dependent Kinase-Like 5 claim 1 , SCN1A claim 1 , SCN2A claim 1 , SCN8A claim 1 , ARX claim 1 , KCNA1 claim 1 , KCNA2 claim 1 , KCNT1 claim 1 , KCNQ2 claim 1 , HCN1 claim 1 , PCDH19 claim 1 , GRIN1 claim 1 , GRIN2A and GRIN2B.3. The method of claim 1 , wherein the epileptic encephalopathy is selected from the group of Dravet syndrome claim 1 , Lennox-Gastaut syndrome claim 1 , Tuberous Sclerosis Complex and seizures associated with mutations in CHD2 claim 1 , Cyclin-Dependent Kinase-Like 5 claim 1 , SCN1A claim 1 , SCN2A claim 1 , SCN8A claim 1 , ARX claim 1 , KCNA1 claim 1 , KCNA2 claim 1 , KCNT1 claim 1 , KCNQ2 claim 1 ...

A CRYSTALLINE 19-NOR C3,3-DISUBSTITUTED C21-N-PYRAZOLYL STEROID

This invention relates to a crystalline 19-nor C3,3-disubstituted C21-pyrazolyl steroid of Formula (I), 145-. (canceled)47. The method of claim 46 , wherein the peak between and including 9.7 to 10.1 is 9.9 degrees in 2θ claim 46 , the peak between and including 11.6 to 12.0 is 11.8 degrees in 2θ claim 46 , the peak between and including 13.2 to 13.6 is 13.4 degrees in 2θ claim 46 , the peak between and including 14.2 to 14.6 is 14.4 degrees in 2θ claim 46 , the peak between and including 14.6 to 15.0 degrees is 14.8 in 2θ claim 46 , the peak between and including 16.8 to 17.2 is 17.0 degrees in 2θ claim 46 , the peak between and including 20.5 to 20.9 is 20.7 degrees in 2θ claim 46 , the peak between and including 21.3 to 21.7 is 21.5 degrees in 2θ claim 46 , the peak between and including 21.4 to 21.8 is 21.6 degrees in 2θ claim 46 , and the peak between and including 22.4 to 22.8 is 22.6 degrees in 2θ.48. The method of claim 46 , wherein the disorder is a neurological disorder.49. The method of claim 48 , wherein neurological disorder is a neurodegenerative disorder or a movement disorder.50. The method of claim 49 , wherein the neurodegenerative disorder is tinnitus.51. The method of claim 49 , wherein the movement disorder is tremor.52. The method of claim 51 , wherein the tremor is essential tremor.53. The method of claim 46 , wherein the disorder is a psychiatric disorder.54. The method of claim 53 , wherein the psychiatric disorder is a mood disorder or a psychotic disorder.55. The method of claim 54 , wherein the mood disorder is a major depressive disorder (MDD).56. The method of claim 54 , wherein the mood disorder is postpartum depression (PPD).57. The method of claim 53 , wherein the psychiatric disorder is an anxiety disorder.58. The method of claim 57 , wherein the anxiety disorder is generalized anxiety disorder.59. The method of claim 54 , wherein the psychotic disorder is bipolar disorder.60. The method of claim 46 , wherein the crystalline solid ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF GLIOBLASTOMA

Provided are compositions that include a platelet-activating factor antagonist, pharmaceutical compositions including the platelet-activating factor antagonist, methods of treating a modulating the proliferation of a glioma or a pathological condition resulting from patient having a glioma. 3. The composition of claim 1 , wherein the compound is an R-enantiomer claim 1 , an S-enantiomer claim 1 , or a combination thereof.4. The composition of claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is in an amount effective to inhibit the growth of a brain tumor or modulate a neurological activity induced by a brain tumor by antagonizing platelet-activating factor claim 1 , and the composition further comprises a pharmaceutically acceptable carrier.5. The composition of claim 4 , wherein the brain tumor is a selected from the group consisting of: a glioblastoma claim 4 , an astrocytoma claim 4 , an oligodendroglioma claim 4 , an ependymal tumor claim 4 , a neuronal tumor and a combination of glial tumors.6. The composition of claim 1 , wherein the pharmaceutically acceptable salt is an acid addition salt.9. The method of claim 7 , wherein the brain tumor is a selected from the group consisting of: a glioblastoma claim 7 , an astrocytoma claim 7 , an oligodendroglioma claim 7 , an ependymal tumor claim 7 , a neuronal tumor and a combination of glial tumors.10. The method of claim 7 , wherein the pharmaceutically acceptable salt is an acid addition salt.13. The method of claim 7 , wherein the therapeutic composition is formulated with an amount of the PAF receptor antagonist effective in reducing or inhibiting a pathological neurological condition associated with a brain tumor in a subject.14. The method of claim 13 , wherein the therapeutic composition is formulated with an amount of the PAF receptor antagonist effective in reducing or inhibiting a seizure associated with glioblastoma in a subject.15. (canceled)16. (canceled)17. (canceled) This ...

NOVEL AFLATOXIN AND FUNGAL INFECTION CONTROL METHODS

The technology provided herein relates to novel methods and compounds for a multi-species pathogen infection control. In particular, the present disclosure pertains to methods of inhibiting the growth of a target pathogen expressing the cysteine-rich secreted protein (CSP), whereby the method comprises contacting said target pathogen with an inhibitor against said CSP, wherein said inhibitor inhibits the CSP expression and/or binds to a protein product of a gene coding CSP. Nucleic acid molecules encoding said inhibitors, vectors and host cells containing the nucleic acids and methods for preparation and producing such inhibitors are also disclosed, as well as the use of said CSP-inhibitors for the control/treatment of diseases associated with a microbial pathogen expressing CSP. 1. A method of inhibiting the growth of a target pathogen expressing the cysteine-rich secreted protein (CSP) , whereby the method comprises contacting said target pathogen with an inhibitor against said CSP , wherein said inhibitor inhibits the CSP expression and/or binds to a protein product of a gene coding CSP.2Aspergillus,Aspergillus flavus, Aspergillus parasiticusAspergillus fumigatus.. The method according to claim 1 , wherein the target pathogen is an aflatoxin-producing fungus and/or a fungus belonging to the phylum Ascomycota claim 1 , optionally a fungus belonging to the order Eurotiales claim 1 , optionally a fungus belonging to the family Trichocomaceae claim 1 , optionally a fungus belonging to the genera of which is optionally selected from the group consisting of and3. The method according to claim 1 , wherein the CSP is coded by an mRNA comprising SEQ ID NO: 1 claim 1 , or a homolog thereof claim 1 , homolog having a sequence identity of at least 60% claim 1 , optionally at least 70% claim 1 , optionally at least 80% claim 1 , optionally at least 85% claim 1 , optionally at least 90% claim 1 , optionally at least 95% claim 1 , optionally at least 96 claim 1 , 97 claim 1 , ...

METHODS FOR TREATING SEIZURES IN EPILEPSY WITH A COMPOSITION COMPRISING CANNABINOIDS

Methods for treating seizures in a subject having epilepsy are provided. The method may comprise administering a pharmaceutical composition comprising CBD and THC to the subject. In some embodiments, the ratio of CBD to THC in the pharmaceutical composition is between about 14:1 and about 17:1. Related uses of the pharmaceutical composition to treat seizures in a subject having epilepsy are also provided. 1. A method for treating seizures in a subject having epilepsy , the method comprising administering a pharmaceutical composition comprising cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC) to the subject , wherein the ratio of CBD to THC in the pharmaceutical composition is between about 14:1 and about 17:1.2. The method of claim 1 , wherein the ratio of CBD to THC in the pharmaceutical composition is between about 15:1 and about 16:1.3Cannabis. The method of claim 1 , wherein the pharmaceutical composition comprises a extract.4Cannabis. The method of claim 3 , wherein the extract is from the Avidekel™ cultivar.5Cannabis. The method of claim 3 , wherein the extract is a whole plant extract.6. The method of claim 1 , wherein the pharmaceutical composition further comprises cannabiochromene (CBC).7. The method of claim 1 , wherein the pharmaceutical composition further comprises at least one terpene.8. The method of claim 1 , wherein the subject is an adult.9. The method of claim 1 , wherein the seizures are drug-resistant seizures.10. The method of claim 1 , wherein the subject has at least one comorbidity of epilepsy and the pharmaceutical composition treats the at least one comorbidity.11. The method of claim 10 , wherein the at least one comorbidity comprises at least one of depression claim 10 , anxiety claim 10 , and Autism Spectrum Disorder.12. The method of claim 1 , wherein the pharmaceutical composition is administered concomitantly with at least one other anti-seizure medication.13. The method of claim 1 , wherein the subject is not concurrently taking ...

Oral film compositions and dosage forms having precise active dissolution profiles

An oral film in an individual unit dose for delivery of one or more actives is disclosed herein, the film having a precisely calculated and controlled active dissolution profile. A wide variety of actives may be used, including, for example, clobazam, diazepam, or riluzole. Also disclosed are methods of treating a variety of diseases and conditions, for example, epilepsy and seizures, by administering the oral film disclosed herein.

EXTRACT OF VICIA FABA BEANS

The extract of beans is prepared by soaking beans in distilled water overnight and then boiling in a water bath to reduce the volume of aqueous extract, which is then homogenized and filtered. The filtrate is concentrated to a smaller volume, lyophilized, and powdered. The lyophilized powder is extracted with hexane to remove oils and lipids. The oil-free lyophilized powder is dissolved in ethanol solvent and extracted for eight hours under reflux, and filtered. The volume of ethanol is reduced by a rotary evaporator, and a first off-white precipitate (sample A-1) is collected, washed with ethanol, and dried at 80° C. Mass spectrometry shows a molecular weight of 200.16447 g mol, and an empirical formula of CHNOis assigned. Intraperitoneal injection of mice with 50 mg/kg of A-1 twenty minutes prior to injection with strychnine protected the mice from strychnine-induced convulsions to the same extent as phenobarbitone (phenobarbital). 18-. (canceled)1019-. (canceled) This application is a division of application Ser. No. 16/145,090, filed Sep. 27, 2018, now pending.The disclosure of the present patent application relates to anticonvulsant compounds of potential use in the treatment of epilepsy or avoidance of epileptic seizures, and particularly to an extract of beans, also known as broad beans, fava beans, or faba beans, and method of extracting the beans to obtain an anticonvulsant.The plant , also known as the broad bean, faba bean, fava bean, etc., is an ancient flowering plant long cultivated in and native to the Mediterranean region and southwestern Asia. It is a legume belonging to the Fabaceae bean family, having a broad, leathery pod and green fruit that mature to a blackish-brown color. can grow in cold and hot countries, withstanding harsh and cold climates, in soils with high salinity and a wide range of pH (4.5-8.3), as well as in clay soils.Broad bean plants are highly susceptible to early summer infestations that can cause discoloration of pods, ...

Methods and compositions for treating a premature stop codon-mediated disorder

Modified tRNAs can be used to express in a mammalian cell a functional gene product encoded by a gene containing a premature stop codon and/or to treat a disease mediated by a premature stop codon.

Methods for controlling seizures by manipulating the levels of microRNA-211 (miR-211) in the brain

Method for controlling for the appearance of seizures in the mammalian brain comprising modifying the abundance of a specific miRNA-miR-211, for uses in preventing seizures and providing a model system to examine the effect of a drug or a treatment to seizures. 1. A method for limiting or enhancing the chance for seizures in a brain of a mammal , the method comprising: introducing into said brain an oligonucleotide including a sequence substantially similar to miR-211 , or a complement thereof.2. The method of claim 1 , wherein said introducing of said oligonucleotide is done by administering to said mammal an externally synthesized oligonucleotide.3. The method of claim 2 , wherein said oligonucleotide is a miR-211 mimetic molecule.4. The method of claim 3 , wherein said mimetic molecule is selected from a group consisting of locked nucleic acid (LNA) claim 3 , 2-O-methyl-blocked Morpholino and phosphorothioate oligonucleotides.5. The method of wherein said oligonucleotide is selected from the group consisting of: SEQ ID No. 1 claim 2 , SEQ ID No. 2 claim 2 , SEQ ID No. 3 claim 2 , SEQ ID No. 4 claim 2 , SEQ ID No. 5 claim 2 , SEQ ID No. 6 claim 2 , or a complement thereof.6. The method of wherein said oligonucleotide is selected from the group consisting of: SEQ ID No. 1 claim 5 , SEQ ID No. 2 claim 5 , or a complement thereof claim 5 , and wherein the mammal is selected from the group of human claim 5 , non-human primate claim 5 , mouse and rat.7. The method of claim 1 , wherein introducing said oligonucleotide is done by transgenic modification claim 1 , AND wherein said mammalian brain is a mammalian brain of a non-human mammal.8. The method of claim 1 , wherein said brain is the brain of a human individual suffering from a seizure related condition.9. The method of claim 8 , wherein said seizure related condition is epilepsy.10. The method of claim 9 , wherein said seizure related condition is refractory OR intractable epilepsy.11. The method of claim 8 , ...

Pharmaceutical Composition Comprising Licarbazepine Acetate

A pharmaceutical composition comprising licarbazepine acetate, especially eslicarbazepine acetate, in combination with suitable excipients, in particular a binder, and a disintegrant. Also disclosed is a granulation process, especially a wet granulation process, for making the pharmaceutical composition.

Compounds and methods for reducing kcnt1 expression

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of KCNT1 RNA in a cell or subject, and in certain instances reducing the amount of KCNT1 protein in a cell or subject. These compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurological condition. Such symptoms and hallmarks include seizures, encephalopathy, and behavioral abnormalities. Non-limiting examples of neurological conditions that benefit from these compounds, methods, and pharmaceutical compositions are epilepsy of infancy with migrating focal seizures (EIMFS), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), West syndrome, and Ohtahara syndrome.

METHODS OF TREATING EPILEPTIC PATIENTS WITH FENFLURAMINE

The present disclosure provides methods of treating and/or preventing symptoms of epilepsy or epileptic encephalopathy where fenfluramine or a pharmaceutically acceptable salt thereof is or has been administered to a patient or population of patients. The present disclosure encompasses a recognition of contraindication of fenfluramine and certain serotonin receptor agonists, particularly a CNS penetrant serotonin receptor antagonist. The present disclosure provides methods where said patients being administered fenfluramine have been warned against co-administration of certain serotonin receptor antagonists, are not co-administered a serotonin receptor antagonist, and/or in which co-administration of a serotonin-receptor antagonist is discontinued. 1. A method of treating epilepsy , the method comprising:administering a therapeutically effective amount of fenfluramine or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the patient is not concurrently being administered a serotonin (5-HT)-receptor antagonist.2. The method of claim 1 , wherein the patient is also characterized by extreme weight loss claim 1 , wasting claim 1 , cachexia and/or loss of appetite.3. The method of claim 1 , wherein the patient is also characterized by a co-morbid psychiatric condition or psychosis.4. (canceled)5. The method of claim 1 , further comprising:administering a therapeutically effective amount of fenfluramine or a pharmaceutically acceptable salt thereof,monitoring the patient for extreme weight loss, wasting, cachexia and/or loss of appetite.6. The method of claim 2 , further comprising:administering an appetite stimulant that is not a serotonin (5-HT)-receptor antagonist.7. (canceled)8. The method of claim 1 , further comprising:providing to the patient instructions that the anti-seizure efficacy of fenfluramine or a pharmaceutically acceptable salt thereof may be reduced by administration of a serotonin receptor antagonist.9. (canceled)10. The ...

COMPOSITIONS AND THEIR USE FOR CONTROLLING THE NERVOUS SYSTEM IN VIVO

Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several drawbacks, including invasive modes of stimulation or slow on/off kinetics. These disadvantages have been overcome by synthesizing a magnetically sensitive actuator, Magneto, comprised of the cation channel, TRPV4, fused to the paramagnetic protein, ferritin. Magneto permits non-invasive magnetic control over neuronal activity by showing remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, the first magnetogenetic control of the nervous system was demonstrated by using Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together, our results present Magneto as a novel actuator capable of remotely controlling circuits associated with complex animal behaviors. 1. A composition comprising a nucleic acid coding for a fusion protein , wherein the fusion protein comprises a channel component or a G-protein coupled receptor (GPCR) and a ferritin component.2. A composition comprising a fusion protein , wherein the fusion protein comprises a channel component a G-protein coupled receptor (GPCR) and a ferritin component.3. The composition of claim 1 , wherein the fusion protein is a single-component magnetogenetic actuator/a genetically encoded actuator.4. The composition of claim 1 , wherein the channel is transient receptor potential vanilloid 4 (TRPV4) or a potassium (K) channel.5. The composition of claim 4 , wherein the potassium (K) channel is TREK-1.6. The composition of claim 1 , wherein the ferritin component comprises at least two subunits of ferritin.7. The composition of claim 1 , wherein the fusion protein further comprises a membrane trafficking signal (TS).8. The composition ...

METHODS FOR GUIDING THERAPY DECISIONS IN SEIZURE DISORDERS

Materials and methods for identifying subjects as being likely or not likely to respond to an interleukin-1β receptor antagonist (IL-1RA) therapy for a seizure disorder, as well as materials and methods for treating subjects identified as being likely to respond to an IL-1RA therapy for a seizure disorder, are provided herein. 114-. (canceled)15. A method for treating a subject having a seizure disorder , comprising identifying the subject as having decreased IL-1RA function as compared to the level of IL-1RA function in corresponding normal subjects who do not have the seizure disorder , and administering to the subject a treatment that attenuates IL-1R inflammatory signaling.16. The method of claim 15 , wherein the treatment comprises an IL-1RA replacement therapy claim 15 , IL-1RA supplementation therapy claim 15 , or IL-1β pathway antagonism.17. The method of claim 15 , wherein the treatment comprises an IL-1RA replacement therapy claim 15 , and wherein the IL-1RA replacement therapy comprises anakinra.to the subject.18. The method of claim 15 , wherein the seizure disorder is FIRES claim 15 , PASS claim 15 , DIRA claim 15 , or MRE.19. The method of claim 15 , wherein the subject is a human child.20. The method of claim 15 , wherein the control level of IL-1RA function is the level of IL-1RA function in corresponding normal subjects who do not have the seizure disorder.21. The method of claim 15 , wherein the determining comprises measuring IL-1RA activity in a biological sample from the subject claim 15 , wherein the biological sample comprises serum claim 15 , serum microvesicles claim 15 , or CSF claim 15 , and determining that the IL-1RA activity in the biological sample is decreased relative to a corresponding control level of IL-1RA activity.22. The method of claim 15 , wherein the determining comprises measuring an inflammatory response in primed and stimulated neutrophils claim 15 , monocytes claim 15 , or PBMCs isolated from the subject claim 15 , and ...

Parenteral carbamazepine formulation

The present invention is directed to a carbamazepine-cyclodextrin inclusion complex useful for the parenteral administration of carbamazepine. The carbamazepine-cyclodextrin inclusion complex is prepared by the admixture of a modified cyclodextrin and carbamazepine in a physiologically acceptable fluid. Modified cyclodextrins include 2-hydroxypropyl-beta-cyclodextrin and sulfoalkyl cyclodextrins. More particularly, the sulfoalkyl cyclodextrins are those described and disclosed in U.S. Pat. Nos. 5,134,127 and 5,376,645. A physiologically acceptable fluid includes sterile isotonic water, Ringer's lactate, D5W (5% dextrose in water), physiological saline, and similar fluids suitable for parenteral administration.

CANNABIDIOL-TYPE CANNABINOID COMPOUND

The present invention relates to a cannabidiol (CBD) type cannabinoid compound for use as a medicament. The CBD-type cannabinoid, 6-hydroxy cannabidivarin (6-OH CBDV), is a metabolite of cannabidivarin (CBDV). The cannabinoid can be produced by synthetic means and a method for the production of 6-OH CBDV is described herein. In addition, disclosed herein are data which demonstrate the efficacy of 6-OH CBDV in a model of disease. 1. A method of treating epilepsy in a subject in need thereof , comprising administering 6-hydroxy cannabidivarin (6-OH CBDV).2. The method of claim 1 , wherein the 6-OH CBDV is in the form of a synthetic compound.3. The method of claim 1 , wherein the 6-OH CBDV is in the form of a pure or isolated compound.4. The method of claim 1 , wherein the dose of 6-OH CBDV is greater than 100 mg/kg/day.5. The method of claim 1 , wherein the dose of 6-OH CBDV is less than 100 mg/kg/day.6. A composition comprising 6-OH CBDV and one or more pharmaceutically acceptable excipients.7. The method of claim 1 , wherein the subject is a mammal.8. The method of claim 1 , wherein the mammal is a human.9. The method of claim 1 , wherein the mammal is a dog.10. A process for the preparation of 6-hydroxy cannabidivarin (6-OH CBDV). This application claims the benefit of International PCT Application No. PCT/GB2020/052944, filed Nov. 18, 2020, and United Kingdom Application No. 1916977.0, filed Nov. 21, 2019. Each of the aforementioned applications are incorporated herein by reference in its entirety.The present invention relates to a cannabidiol (CBD) type cannabinoid compound for use as a medicament.The CBD-type cannabinoid, 6-hydroxy cannabidivarin (6-OH CBDV), is a metabolite of cannabidivarin (CBDV).The cannabinoid can be produced by synthetic means.Disclosed herein are data which demonstrate the efficacy of 6-OH CBDV in a model of disease. In addition, a method for the production of 6-OH CBDV is described.Cannabinoids are natural and synthetic compounds ...

TREATMENT FOR EPILEPSY

The present invention discloses isoquinolines and 1H-2-Benzopyranes and their use in the treatment and prevention in epilepsy and other seizures. The present invention further discloses methods to screen isoquinoline- and 111- 2-Benzopyran- like molecules as pharmaceutically active compounds. 12-. (canceled)6. The method according to claim 3 , which comprises providing an isoquinoline or 1H-2-Benzopyran moiety and testing the compound for antiseizure activity.7. The method according to claim 3 , wherein the compound with a isoquinoline or 1H-2-Benzopyran moiety is TMC-120A claim 3 , TMC-120B claim 3 , TMC-120C claim 3 , penicisochroman G claim 3 , ustusorane B claim 3 , 7-methylfuro[3 claim 3 ,2-h]isoquinoline-3(2H)-one) claim 3 , and (2-(7-methyl-2 claim 3 ,3-dihydrofuro[3 claim 3 ,2-h]isoquinoline-2-yl)-propan-2-ol).8. The method according to claim 3 , wherein halimide and/or plinabulin is added to said compound for testing antiseizure activity.9. The method according to claim 3 , wherein the isoquinoline or 1H-2-Benzypuran is a compound as depicted in and/or 2 claim 3 , with modified molecular structure or stereochemistry.10. The method according to claim 3 , wherein anti-seizure activity is determined in a zebrafish model.11. The method according to claim 3 , wherein anti-seizure activity is further determined in a mammalian model.12. The method according to claim 3 , further comprising the step of testing the compound for a side effect.13. The method according to claim 3 , further comprising the step of formulating a compound with determined anti-seizure activity into a pharmaceutical composition with an acceptable carrier claim 3 , for use in the treatment of epilepsy.14. A method for the treatment or prevention of epilepsy comprising administering to a subject in need thereof an isoquinoline or 1H-2-benzopyran selected from TMC-120A claim 3 , TMC-120B claim 3 , TMC-120C claim 3 , penicisochroman G claim 3 , ustusorane B claim 3 , 7-methylfuro[3 claim 3 ,2-h] ...

GANAXOLONE FOR USE IN TREATMENT OF STATUS EPILEPTICUS

This invention relates to methods for treating status epilepticus by administering to the subject in need thereof an intravenous bolus of ganaxolone and a continuous intravenous infusion of a neurosteroid. The method provides SE suppression and continued suppression of SE. 154-. (canceled)55. A method of treating status epilepticus (SE) , comprising administering to a subject in need thereof an effective amount of ganaxolone to suppress SE for a period of at least 8 hours , wherein the effective amount of ganaxolone is administered as an intravenous bolus plus continuous infusion to produce and maintain a ganaxolone plasma concentration of at least about 500 ng/ml for at least about 8 hours , the amount of ganaxolone infused into said subject by said continuous infusion is decreased at least once while the ganaxolone plasma concentration of at least about 500 ng/ml is maintained; and the total daily dose of ganaxolone administered is from about 500 mg to about 900 mg.56. The method of claim 55 , wherein the intravenous bolus produces a ganaxolone plasma concentration in the subject of at least about 500 ng/ml to about 1000 ng/ml.57. The method of claim 55 , wherein the continuous intravenous infusion produces a ganaxolone plasma concentration in the subject of at least about 500 ng/ml to about 1000 ng/ml for at least about 8 hours.58. The method of claim 55 , wherein the intravenous bolus comprises about 5 mg to about 40 mg of ganaxolone.59. The method of claim 58 , wherein the intravenous bolus comprises about 30 mg of ganaxolone.60. The method of claim 55 , wherein the continuous intravenous infusion comprises infusion of about 20 mg of ganaxolone per hour to about 80 mg of ganaxolone per hour.61. The method of claim 55 , wherein about 80 mg of ganaxolone per hour are infused into the subject at the initiation of the continuous intravenous infusion and for at least about 2 hours thereafter.62. The method of claim 61 , wherein the amount of ganaxolone administered ...

Protein based cannabis compositions

Described herein are novel compositions comprising a cannabis component selected from the group consisting of: a cannabinoid, a flavonoid and a terpenoid; and a protein, selected from the group consisting of whey and a plant protein. According to an embodiment, the cannabis component is non-covalently bound to the whey or to the plant protein. The plant protein may be selected from the group consisting of: soy protein, pea protein, rice protein, hemp protein, and hops protein or other plant derived protein.

HIGH CONCENTRATION MEDICANT SOLUTIONS FOR TREATING NEUROLOGICAL DISORDERS

Highly concentrated solutions are disclosed along with methods of inhibiting and/or ameliorating functional neurological disorders of the brain. The method may include administering directly to a brain of a subject a medicament multiple times over a time period of at least two days. The medicament may include a half-life of less than 2 hour in the cerebrospinal fluid. The method may include inhibiting and/or ameliorating a functional neurological disorder of the brain using the medicant. 1. A method of inhibiting and/or ameliorating functional neurological disorders of a brain in a subject , comprising:administering directly to a brain of a subject a medicament multiple times over a time period of at least two days, wherein the medicament exhibits a half-life of less than 24 hours in cerebrospinal fluid; thereby inhibiting and/or ameliorating a functional neurological disorder.2. The method of claim 1 , wherein the medicament comprises valproic acid or pharmaceutically active derivatives thereof and the half-life is 16 hours or less.3. The method of claim 1 , wherein the medicament is administered via a catheter claim 1 , to cerebrospinal fluid of the subject claim 1 , and the functional neurological disorder selected from the group consisting of Epilepsy claim 1 , Status Epilepticus claim 1 , Bipolar claim 1 , Bipolar Spectrum Disorder claim 1 , Post Traumatic Stress Disorder or Other Epilepsy claim 1 , Bipolar Spectrum and Anxiety Related Disorder.4. The method of claim 1 , wherein the medicament exhibits a half-life of less than about 2 hours in cerebrospinal fluid claim 1 , and wherein during treatment the medicament has a concentration in the cerebrospinal fluid of between about 1 microgram/ml to 500 micrograms/ml.5. The method of claim 4 , wherein the medicament comprises valproic acid or pharmaceutically active derivatives thereof claim 4 , and wherein during treatment the medicament has a concentration in the cerebrospinal fluid of between 2 microgram/mL to ...

Ganaxolone formulation and use thereof

In certain embodiments, the invention is directed to composition comprising stable particles comprising ganaxolone, wherein the volume weighted median diameter (D50) of the particles is from about 50 nm to about 500 nm.

5HT AGONISTS FOR TREATING DISORDERS

Provided, inter alia, are methods for treating an epilepsy disorder using a 5HT receptor agonist, or a pharmaceutically acceptable salt thereof. 158.-. (canceled)59. A method of treating an epilepsy disorder , said method comprising administering to a subject in need thereof a therapeutically effective amount of a 5HT receptor agonist , or a pharmaceutically acceptable salt thereof , wherein said epilepsy disorder is Dravet Syndrome and wherein the 5HT receptor agonist is a small molecule which agonizes a 5-HTreceptor and is suitable for the treatment of obesity.60. The method of claim 59 , wherein said small molecule is lorcaserin.61. The method of claim 60 , wherein the subject in need of treatment for epilepsy suffers from a cardiovascular disease or has a ketogenic diet.62. The method of claim 60 , wherein said subject is resistant to treatment with a serotonin reuptake inhibitor.63. The method of claim 60 , wherein said subject is susceptible to side effects when administered a serotonin reuptake inhibitor.64. The method of claim 63 , wherein said serotonin reuptake inhibitor is fenfluramine.65. The method of claim 60 , wherein said administration of said 5HT receptor agonist reduces or prevents myoclonus seizures or status epilepticus in said subject when compared to the absence of 5HT receptor agonist.66. The method of claim 60 , wherein said administration of said 5HT receptor agonist inhibits compulsive behavior or reduces the incidence of unprovoked seizures in said subject when compared to the absence of said 5HT receptor agonist.67. The method of claim 60 , wherein said 5HT receptor agonist is co-administered with an anti-epileptic drug (AED) or is an adjunctive therapy with an anti-epileptic drug (AED).68. The method of claim 67 , wherein said AED is acetazolamide claim 67 , benzodiazepine claim 67 , cannabadiol claim 67 , carbamazepine claim 67 , clobazam claim 67 , clonazepam claim 67 , eslicarbazepine acetate claim 67 , ethosuximide claim 67 , ...

METHOD OF REDUCTION IN CONVULSIVE SEIZURE FREQUENCY

A method of reducing convulsive seizure frequency in a human patient diagnosed with Dravet syndrome, comprising administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base, acid or amine thereof, and repeating the administering over a period of days until the patient exhibits a significant reduction (e.g., 40% or greater) from baseline in convulsive seizure frequency. In some embodiments of the method, convulsive seizures are completely eliminated for 10 days or more, 20 days or more, 30 days or more, 50 days or more, 100 days or more. 1. A method of treating a patient diagnosed with Dravet syndrome , comprising:administering to the patient a therapeutically effective dose of fenfluramine or a pharmaceutically acceptable salt, base or acid thereof; andrepeating the administering over a period of days until the patient exhibits a reduction from baseline in convulsive seizure frequency of 40% or more.2. The method as claimed in claim 1 , wherein the fenfluramine is the only active ingredient administered to the patient.3. The method of claim 1 , further comprising:administering a co-therapeutic agent.4. The method of claim 3 , wherein the co-therapeutic agent is selected from the group consisting of claim 3 , carbamazepine claim 3 , ethosuximide claim 3 , fosphenytoin claim 3 , lamotrigine claim 3 , levetiracetam claim 3 , phenobarbital claim 3 , topiramate claim 3 , valproic acid claim 3 , valproate claim 3 , verapamil claim 3 , and benzodiazepines such as clobazam claim 3 , clonazepam claim 3 , diazepam claim 3 , lorazepam claim 3 , and midazolam and a pharmaceutically acceptable salt or base thereof.5. The method of claim 4 , wherein the co-therapeutic agent is a combination of stiripentol claim 4 , valproate and clobazam.6. The method of claim 1 , wherein the co-therapeutic agent is cannabidiol.7. The method of claim 1 , wherein the administering is over a period of months claim 1 , and the co- ...

PHARMACEUTICAL COMPOSITIONS

Novel treatment methods of controlling cell hyperexcitability occurring in a neurological disease or disorder associated with epileptogenesis or cardiac disorder are disclosed herein. Novel pharmaceutical compositions comprising adenosine or adenosine agonists and at least one selected from phytocannabinoids and terpenes are disclosed. 1. A method of treating a disorder in a subject in need of treatment comprising the steps of:administering to the subject a substance selected from the group consisting of adenosine, an adenosine analog, an adenosine agonist, an adenosine transport inhibitor, modulation of adenosine levels at biophase, a serotonin receptor agonist and a combination thereof; andadministering to the subject at least one selected from the group consisting of a phytocannabinoid and a terpene.2. The method of wherein the disorder is selected from the group consisting seizure disorders and cardiac disorders.3. The method of wherein the disorder is a seizure disorder.4. The method of wherein the disorder is selected from the group consisting of hippocampal neural circuit hyperexcitability claim 1 , intractable epilepsy claim 1 , Dravet's syndrome claim 1 , febrile seizures claim 1 , autism spectrum disorder and attention deficit hyperactivity disorder.5. The method of wherein the substance is selected from the group consisting of substances used to treat epilepsy claim 1 , Bechet' syndrome claim 1 , Dravet Syndrome claim 1 , Lennox Gastaut Syndrome claim 1 , intractable childhood epilepsies claim 1 , Autism claim 1 , Fragile x syndrome claim 1 , Angelman's syndrome claim 1 , multiple sclerosis claim 1 , migraines claim 1 , seizures in Alzheimer's disease claim 1 , posttraumatic chronic pain claim 1 , chronic traumatic encephalopathy claim 1 , neuropathic pain claim 1 , traumatic brain injury claim 1 , cluster headaches claim 1 , fibromyalgia claim 1 , arthritis claim 1 , pancreatitis claim 1 , gastritis claim 1 , inflammatory bowel syndrome claim 1 , Crohn's ...

ION CHANNEL MODULATORS

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein. 13. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris cyclobutyl optionally substituted with one or more R.14. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris Chaloalkyl.15. The compound of any one of - and , or a pharmaceutically acceptable salt thereof , wherein Ris CF.16. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris phenyl.17. The compound of any one of - and - , or a pharmaceutically acceptable salt thereof , wherein Ris Calkyl and Ris hydrogen or Calkyl.18. The compound of any one of - and - , or a pharmaceutically acceptable salt thereof , wherein Rand Rare each Calkyl.19. The compound of any one of - and - , or a pharmaceutically acceptable salt thereof , wherein Rand Rare each methyl.20. The compound of any one of - and - , or a pharmaceutically acceptable salt thereof , wherein Ris methyl and Ris hydrogen.21. The compound of any one of - and - , or a pharmaceutically acceptable salt thereof , wherein Rand Rare each hydrogen.22. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris —CF—OR.23. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris Calkyl optionally substituted with cyclopropyl.24. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein Ris cyclopropyl.25. The compound of any one of - , or a pharmaceutically acceptable ...

Method and composition for acute treatment of seizures

A nasal spray composition and method for treating convulsive seizures, including epileptic seizures, and also autism behavioral events. In certain embodiments, the nasal spray composition contains delta-9-tetrahydrocannabinol, cannabidiol and, optionally, terpenes such as linalool.

METHOD AND COMPOSITION FOR TREATING EPILEPSY

A method of treating a subject suffering from epilepsy includes administering an effective amount of a cholecystokinin-2 receptor antagonist or a pharmaceutical acceptable salt thereof to the subject. A pharmaceutical composition includes the cholecystokinin-2 receptor antagonist or a pharmaceutical acceptable salt thereof as active ingredient, one or more antiepileptic compounds, and a pharmaceutically acceptable excipient. 1. A method of treating a subject suffering from epilepsy comprising the step of administering an effective amount of a cholecystokinin-2 receptor antagonist or a pharmaceutical acceptable salt thereof to the subject.3. The method of claim 2 , wherein the cholecystokinin-2 receptor antagonist has a structure of Formula (Ia) with Rbeing a linear or branched chain C1 to C4 alkyl group claim 2 , or a substituted or unsubstituted aryl group; Rbeing a substituted or unsubstituted aryl group claim 2 , or a heteroaryl; and Rbeing a methyl group claim 2 , an ethyl group claim 2 , a methylamino group or an ethylamino group.6. The method of claim 1 , wherein the cholecystokinin-2 receptor antagonist is administered in combination with one or more antiepileptic compounds to the subject.7. The method of claim 6 , wherein the antiepileptic compound is selected from the group consisting of primidone claim 6 , diazepam claim 6 , perampanel claim 6 , tiagabine claim 6 , methsuximide claim 6 , ethosuximide claim 6 , stiripentol claim 6 , phenobarbital sodium claim 6 , felbamate claim 6 , acetazolamide claim 6 , brivaracetam claim 6 , benzobarbital claim 6 , phenytoin sodium claim 6 , clobazam claim 6 , fosphenytoin sodium claim 6 , ezogabine claim 6 , lacosamide claim 6 , eslicarbazepine claim 6 , topiramate claim 6 , oxcarbazepine claim 6 , zonisamide claim 6 , lamotrigine claim 6 , carbamazepine claim 6 , clonazepam claim 6 , vigabatrin claim 6 , levetiracetam claim 6 , divalproex sodium claim 6 , valproic acid claim 6 , lorazepam claim 6 , clorazepate claim 6 ...

COMPOSITIONS AND METHODS FOR TREATING CONDITIONS ASSOCIATED WITH GAIN-OF-FUNCTION MUTATIONS IN KCNT1

Compositions and methods suitable for treating diseases and conditions associated excessive neuronal excitability, and/or diseases associated with gain-of-function mutations in KCNT1. More specifically, antisense oligonucleotides specific for KCNT1 and their use for treating diseases and conditions associated with excessive neuronal excitability and/or gain-of-function mutations of KCNT1. 1. An antisense oligonucleotide comprising a sequence of nucleobases that is complementary to a target region in KCNT1.2. The antisense oligonucleotide of claim 1 , wherein the target region is within the KCNT1 sequence set forth in SEQ ID NO:1 or a variant thereof having at least or about 75% claim 1 , 76% claim 1 , 77% claim 1 , 78% claim 1 , 79% claim 1 , 80% claim 1 , 81% claim 1 , 82% claim 1 , 83% claim 1 , 84% claim 1 , 85% claim 1 , 86% claim 1 , 87% claim 1 , 88% claim 1 , 89% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% or 99% sequence identity thereto.3. The antisense oligonucleotide of or claim 1 , wherein the antisense oligonucleotide hybridizes to the pre-mRNA and/or mRNA of KCNT1.4. The antisense oligonucleotide of any one of - claim 1 , wherein the target region is within or spans all or a part of an exon claim 1 , intron claim 1 , an intron/exon junction claim 1 , a 3′-untranslated region (UTR) claim 1 , a 5′-UTR claim 1 , the translation initiation site and/or the translation termination site.5. The antisense oligonucleotide of any one of - claim 1 , wherein the antisense oligonucleotide is an allele-specific oligonucleotide.6. The antisense oligonucleotide of any one - claim 1 , wherein the target region spans a nucleotide selected from among nucleotide 5236 claim 1 , 39323 claim 1 , 53882 claim 1 , 55173 claim 1 , 73279 claim 1 , 73631 claim 1 , 80231 or 91871 of SEQ ID NO:1.7. The antisense oligonucleotide of claim 6 , wherein the antisense oligonucleotide specifically hybridizes ...

USE OF CANNABINOIDS IN THE TREATMENT OF SEIZURES AS ASSOCIATED WITH LENNOX-GASTAUT SYNDROME

The present invention relates to the use of cannabidiol (CBD) in the treatment of patients with Lennox-Gastaut syndrome (LGS) who are deemed to be treatment failures on their existing medication. In particular the use of CBD was found to provide a statistically significant reduction in both drop seizures and total seizure frequency in patients who have tried and failed anti-epileptic drugs (AEDs) or those who were currently taking AEDs but have uncontrolled seizures. Preferably the AEDs which have been shown to be treatment failures are one or more of rufinamide, lamotrigine, topiramate and/or felbamate. Preferably the CBD used is in the form of a highly purified extract of cannabis such that the CBD is present at greater than 98% of the total extract (w/w) and the other components of the extract are characterised. In particular the cannabinoid tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 0.15% (w/w) and the propyl analogue of CBD, cannabidivarin, (CBDV) is present in amounts of up to 1%. Alternatively, the CBD may be a synthetically produced CBD. 1. A method of treating seizures associated with Lennox-Gastaut syndrome (LGS) comprising administering cannabidiol (CBD) to a subject diagnosed with LGS , wherein the subject is deemed to be a treatment failure on one or more anti-epileptic drugs (AEDs).2. The method of claim 1 , wherein the one or more AEDs are rufinamide claim 1 , lamotrigine claim 1 , felbamate claim 1 , or a combination thereof.3. The method of claim 1 , wherein the CBD is in the form of a highly purified extract of cannabis which comprises at least 98% (w/w) CBD.4. The method of claim 1 , wherein the CBD is present as a synthetic compound.5. The method of claim 3 , wherein the highly purified extract comprises less than 0.15% THC.6. The method of claim 3 , wherein the extract further comprises up to 1% CBDV.7. The method of claim 1 , wherein the dose of CBD is below 50 mg/kg/day.8. The method of claim 1 , ...

N-optionally substituted aryl-2-oligomer-3-alkoxypropionamides

The invention relates to (among other things) N-optionally substituted aryl-2-oligomer-3-alkoxypropionamides and compositions comprising the same. A compound of the invention, when administered by any of a number of administration routes, exhibits one or more advantages over corresponding compounds lacking the oligomer.

CANNABINOID DERIVATIVES AS PHARMACEUTICALLY ACTIVE COMPOUNDS AND METHODS OF PREPARATION THEREOF

The present invention relates to a group of cannabinoid derivatives as pharmaceutically active compounds and methods of preparation thereof. The cannabinoid derivatives of the invention are analogues of cannabidiol (CBD). CBD is a non-psychoactive cannabinoid which has been used to treat various diseases and disorders. While such treatments hold promise, there remains a need in the art for more effective treatments and this has been brought about by way of the cannabinoid derivatives of the invention 3. A pharmaceutical composition comprising a compound of or salt thereof.4. A pharmaceutical composition as claimed in claim 3 , wherein the pharmaceutical composition is selected from a tablet claim 3 , a capsule claim 3 , a granule claim 3 , a powder for inhalation claim 3 , a sprinkle claim 3 , an oral solution and a suspension.5. A pharmaceutical composition as claimed in claim 3 , wherein the composition additionally comprises one or more of: an excipient selected among a carrier claim 3 , an oil claim 3 , a disintegrant claim 3 , a lubricant claim 3 , a stabilizer claim 3 , a flavouring agent claim 3 , an antioxidant claim 3 , a diluent and another pharmaceutically effective compound.6. (canceled)7. A method of treating epilepsy in a mammal in need thereof comprising administering a pharmaceutical preparation comprising a compound of or salt thereof.8. (canceled)9. A process for the production of a compound of general Formula I comprising reacting a resorcinol unit of Structure 1a-j via a Friedel-Crafts 1 claim 1 ,4-addition to produce compounds of Structures 2a to 2j or 3a to 3j followed by subsequent steps to produce the compounds of general Formula I via intermediates.10. An intermediate formed in the process of the production of a compound of general Formula I.11. A pharmaceutical composition comprising a compound of or salt thereof.12. A pharmaceutical composition as claimed in claim 11 , wherein the pharmaceutical composition is selected from a tablet claim ...

CONJOINT THERAPY FOR TREATING SEIZURE DISORDERS

In certain embodiments, the present disclosure is directed to methods and uses for treating seizure disorders in a human in need thereof, wherein the methods and uses comprise conjointly administering N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (Compound A) and an antiseizure medication (ASM) to the human in amounts that are therapeutically effective when conjointly administered. The present disclosure is further directed to various improved methods of therapy and administration of Compound A. 1. A method of treating a seizure disorder in a human in need thereof , comprising conjointly administering Compound A and an antiseizure medication (ASM) to the human in amounts that are therapeutically effective when conjointly administered;wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide.2. A method of reducing the amount of an antiseizure medication (ASM) that is required for therapeutic efficacy in a human suffering from a seizure disorder , comprising administering to the human , conjointly with the ASM , an amount of Compound A that is effective to achieve such reduction when administered with the ASM;wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide.3. A method of reducing the amount of Compound A that is required for therapeutic efficacy in a human suffering from a seizure disorder , comprising administering to the human , conjointly with Compound A , an amount of an antiseizure medication (ASM) that is effective to achieve such reduction when administered with Compound A;wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide.4. The method of any one of - , which comprises enhancing the opening of a Kv7 potassium channel in the human.5. A method of enhancing the opening of a Kv7 potassium channel in a human , comprising conjointly ...

TREATMENT OF EXCITOTOXICITY-RELATED CONDITIONS

Disclosed herein are methods for treating or preventing an excitotoxicity-related condition, optionally a condition associated with seizures and/or resulting from or associated with a cerebral ischemic event, comprising administering to a subject in need an effective amount of an inhibitor of Lim-domain kinase 1 (LIMK1). Also provided are methods for treating or preventing seizures and for reducing excitotoxicity in neurons and/or protecting neurons from excitotoxicity. 1. A method for treating or preventing an excitotoxicity-related condition in a subject , the method comprising administering to the subject an effective amount of an inhibitor of Lim-domain kinase 1 (LIMK1).226-. (canceled)27. The method according to claim 1 , wherein the excitotoxicity-related condition is associated with seizures.28. The method according to claim 27 , wherein the seizures are absence seizures claim 27 , tonic seizures claim 27 , atonic seizures claim 27 , clonic seizures claim 27 , myoclonic seizures or tonic-clonic seizures.29. The method according to claim 1 , wherein the excitotoxicity-related condition results from or is associated with a cerebral ischemic event.30. The method according to claim 29 , wherein the cerebral ischemic event comprises a traumatic brain injury or stroke.31. The method according to claim 1 , wherein the excitotoxicity-related condition is epilepsy.32. The method according to claim 1 , wherein treating or preventing the excitotoxicity-related condition comprises reducing the severity of a seizure or of seizures over time claim 1 , increasing the latency to develop a seizure or seizures over time claim 1 , and/or reducing the frequency of seizures.33. The method according to claim 1 , wherein treating or preventing the excitotoxicity-related condition comprises reducing excitotoxicity in neurons and/or for protecting neurons from excitotoxicity.34. A method for treating or preventing seizures in a subject in need thereof claim 1 , the method comprising ...