METHODS AND KITS FOR TREATING CLUSTER HEADACHE DISORDERS

The invention features methods and kits employing bromolysergide in therapies for the treatment of cluster headache disorders. 1. A method of treating a recurrent cluster headache disorder in a subject in need thereof , said method comprising administering 2-bromolysergic acid diethylamide , or a pharmaceutically acceptable salt thereof , to said subject in an amount sufficient to treat said recurrent cluster headache disorder.2. A method of treating a chronic cluster headache disorder in a subject in need thereof , said method comprising administering 2-bromolysergic acid diethylamide , or a pharmaceutically acceptable salt thereof , to said subject in an amount sufficient to treat said chronic cluster headache disorder.3. A method of treating an episodic cluster headache disorder in a subject in need thereof , said method comprising administering 2-bromolysergic acid diethylamide , or a pharmaceutically acceptable salt thereof , to said subject in an amount sufficient to treat said episodic cluster headache disorder.4. A method of extending the remission period of a subject with a cluster headache disorder , said method comprising administering 2-bromolysergic acid diethylamide , or a pharmaceutically acceptable salt thereof , to said subject while said subject is in remission in an amount sufficient to extend said remission period.5. The method of claim 4 , wherein said cluster headache disorder is episodic cluster headache disorder.6. The method of claim 4 , wherein said cluster headache disorder is chronic cluster headache disorder.7. The method of claim 4 , wherein said subject is experiencing autonomic symptoms characteristic of an impending cluster headache attack.8. The method of claim 1 , wherein a dose of from 20 to 50 μg/kg of 2-bromolysergic acid diethylamide claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is administered to said subject.9. The method of claim 8 , wherein two doses of from 20 to 50 μg/kg of 2-bromolysergic acid ...

VETERINARY ANTI-PROLACTIN COMPOSITION FOR RUMINANTS

The present invention relates to a veterinary anti-prolactin composition to be administered to ruminants. Said composition includes at least one anti-prolactin compound which is an agonist for dopamine receptors and which is particularly useful for preventing and/or reducing the harmful effects in ruminants linked to use for a shortened dry period. Said composition is particularly useful for preventing and/or reducing metabolic diseases and/or reproductive disorders when lactation is resumed. The use of the veterinary anti-prolactin composition according to the invention does not adversely affect the milk-producing ability and/or the milk quality of the treated ruminants 119.-. (canceled)20. A method for preventing and/or reducing the deleterious effects related to the implementation of a shortened dry period in ruminants , wherein said method comprises administration of a veterinary composition comprising at least one compound having an anti-prolactin dopamine receptor agonist activity , wherein said deleterious effects are selected in the group consisting of metabolic diseases , reproductive disorders , immune status or hepatic functions disorders when lactation is resumed , and bad health of the newborn.21. The method according to claim 20 , wherein said method is for preventing and/or reducing metabolic diseases and/or reproductive disorders when lactation is resumed.22. A method for a decrease of the dry period of ruminants by administering to a ruminant a veterinary composition comprising at least one compound having an anti-prolactin dopamine receptor agonist activity.23. The method according to claim 20 , wherein the composition is administered to the ruminant at the time of the implementation of and/or during the dry period.24. The method according to claim 20 , wherein the composition is administered in a single treatment and/or in repeated treatments.25. The method according to claim 20 , wherein the composition is administered at doses from about 8 to 10 ...

NOVEL ISO-ERGOLINE DERIVATIVES

Provided herein are novel iso-ergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alphaand/or the alphareceptors using the compounds and compositions disclosed herein. 2. The compound of claim 1 , wherein Ris hydrogen or (C-C) alkyl substituted with one or more fluorine atoms claim 1 , n is 0 claim 1 , Ris hydrogen or (C-C) alkyl claim 1 , Ris substituted alkyl or —NRR claim 1 , Ris methyl substituted with one or more fluorine atoms and Ris hydrogen claim 1 , substituted alkyl claim 1 , substituted acyl or —CONRR.3. The compound of claim 1 , wherein Ris hydrogen claim 1 , methyl or methyl substituted with one or more fluorine atoms claim 1 , Ris alkyl claim 1 , halo claim 1 , —OR claim 1 , n is 1 claim 1 , Ris hydrogen claim 1 , methyl or allyl claim 1 , Ris substituted alkyl or —NRR claim 1 , Ris methyl substituted with one or more fluorine atoms and Ris hydrogen claim 1 , substituted alkyl claim 1 , substituted acyl or —CONRR.4. The compound of claim 1 , wherein Ris hydrogen claim 1 , methyl or methyl substituted with one or more fluorine atoms claim 1 , n is 0 claim 1 , Ris hydrogen claim 1 , methyl or allyl claim 1 , Ris substituted alkyl or —NRR claim 1 , Ris methyl substituted with one or more fluorine atoms and Ris hydrogen claim 1 , substituted alkyl claim 1 , substituted acyl or —CONRR.9. The compound of claim 1 , wherein Ris hydrogen claim 1 , n is 0 claim 1 , Ris allyl claim 1 , Ris —NRRor ...

Lisuride, Terguride and Derivatives Thereof for Use in the Prophylaxis and/or Treatment of Fibrotic Changes

The present invention relates to the use of 5-HTreceptor antagonists and in particular of 8-α-ergolines such as lisuride, terguride and the derivatives thereof as 5-HTand 5-HTreceptor antagonists and antioxidants in preferably higher-dosed and preferably continuous use for the treatment, progression prophylaxis and general prophylaxis of organ fibroses and other pathological organ remodeling caused by mesenchymal proliferation 2. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to for extending the life of the organism.3. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 1 , whereby during the treatment time claim 1 , at least 80% of the time claim 1 , preferably at least 100% of the treatment time claim 1 , the 5-HT- and/or 5-HT-receptor occupancy in the target organ is at least 90%.4. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 3 , whereby during the entire treatment time claim 3 , the 5-HT- and/or 5-HT-receptor occupancy in the target organ is complete.5. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 1 , whereby the active ingredient level in the systemic circulation of the organism during the treatment time claim 1 , at least 80% of the time claim 1 , preferably 100% of the time continuously claim 1 , is at least 5 pg/ml claim 1 , more preferably at least 100 pg/ml claim 1 , more preferably at least 200 pg/ml claim 1 , and most preferably 300-500 pg/ml.6. Lisuride or terguride or a derivative of general formula (I) for use in the prophylaxis and/or treatment according to claim 1 , wherein the administration is carried out at a dose of 0.01 to 5.0 mg per day claim 1 , preferably 0.15 to 3.0 mg per day claim 1 , and most preferably 0.25 to 1.0 mg per day.7. Lisuride or ...

NOVEL ISO-ERGOLINE DERIVATIVES

Provided herein are novel iso-ergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alphaand/or the alphareceptors using the compounds and compositions disclosed herein. 214-. (canceled)16. The method of claim 15 , wherein the compound selectively agonizes the 5-HTreceptor over the 5-HTreceptor in a ratio of about 4:1.17. The method of claim 15 , wherein the compound selectively agonizes the 5-HTreceptor over the 5-HTreceptor in a ratio of about 30:1.1924-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/531,416, filed Jun. 22, 2012 which claims priority under 35 U.S.C. §119(e) from U.S. Provisional Application Ser. No. 61/577,563, filed Dec. 19, 2011, which are hereby incorporated by reference in their entirety.Provided herein are novel isoergoline analogs and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alphaand/or ...

NITROGENATED AROMATIC HETEROCYCLIC DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT USING SAME

A nitrogen-containing aromatic heterocyclic derivative in which a nitrogen atom of an indenocarbazole skeleton optionally having a hetero atom or an indenoindole skeleton optionally having a hetero atom is bonded to a dibenzofuran or a dibenzothiophene directly or indirectly. The derivative realizes an organic EL device with a high emission efficiency and a long lifetime. 2: The aromatic heterocyclic derivative according to claim 1 , whereinW of formulae (1-1) and (1-2) represents a single bond, andZ of formulae (1a) and (1b) represents a single bond.7: The aromatic heterocyclic derivative according to claim 1 , wherein Lrepresents a single bond.9. (canceled)10: The aromatic heterocyclic derivative according to claim 1 , wherein X represents an oxygen atom.11: The aromatic heterocyclic derivative according to claim 1 , wherein X represents a sulfur atom.12: The aromatic heterocyclic derivative according to claim 1 , wherein X represents CRR.13: The aromatic heterocyclic derivative according to claim 1 , wherein X represents SiRR.14: The aromatic heterocyclic derivative according to claim 1 , wherein Y represents an oxygen atom.15: The aromatic heterocyclic derivative according to claim 1 , wherein Y represents a sulfur atom.16: The aromatic heterocyclic derivative according to claim 1 , wherein Lis bonded to a carbon atom at 4-position of the structure represented by formula (1c).17. A material for organic electroluminescence device claim 1 , comprising the aromatic heterocyclic derivative according to .18: A hole transporting material for organic electroluminescence device claim 1 , comprising the aromatic heterocyclic derivative according to .19: An organic electroluminescence device claim 1 , comprising:a light emitting layer, andorganic thin film layers between an anode and a cathode,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein at least one of the organic thin film layers comprises the aromatic heterocyclic derivative according to .'}20: The ...

VMAT2 INHIBITORS FOR TREATING NEUROLOGICAL DISEASES OR DISORDERS

Methods are provided herein for treating agitation in a subject who has Alzheimer's disease comprising administering a VMAT2 inhibitor to a subject in need thereof. VMAT2 inhibitors useful in the methods provided herein include tetrabenazine and (S)-2-Amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester. 1. A method for treating mania in a mood disorder in a subject comprising administering to the subject a selective VMAT2 inhibitor.2. A method for treating mania in a mood disorder in a subject comprising administering to the subject a VMAT2 inhibitor selected from:tetrabenazine (3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one);(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (R,R,R DHTBZ), or a precursor thereof;(S)-2-Amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester;[(2R,3S,11bR)-9,10-Dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido[2,1-a]isoquinolin-2-yl]methanol, or a precursor thereof; and{'sub': 6', '6, '3-isobutyl-9,10-d-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (d-TBZ); or'}an isotopic variant, a pharmaceutically acceptable salt, or a polymorph thereof.3. The method of claim 1 , wherein the VMAT2 inhibitor is (S)-2-Amino-3-methyl-butyric acid (2R claim 1 ,3R claim 1 ,11bR)-3-isobutyl-9 claim 1 ,10-dimethoxy-1 claim 1 ,3 claim 1 ,4 claim 1 ,6 claim 1 ,7 claim 1 ,11b-hexahydro-2H-pyrido[2 claim 1 ,1-a]isoquinolin-2-yl ester or an isotopic variant claim 1 , a pharmaceutically acceptable salt claim 1 , or a polymorph thereof.4. The method of claim 3 , wherein the VMAT2 inhibitor is (S)-(2R claim 3 ,3R claim 3 ,11bR)-3-isobutyl-9 claim 3 ,10-dimethoxy-2 claim 3 ,3 claim 3 ,4 claim 3 ,6 claim 3 ,7 claim 3 ,11b-hexahydro-1H-pyrido[2 claim 3 ,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4- ...

ILOPERIDONE METABOLITE FOR USE IN THE TREATMENT OF PSYCHIATRIC DISORDERS

R-P88 is used for the treatment of disorders amenable to treatment with an atypical antipsychotic. 1. A method of treating a patient suffering from a psychiatric disorder that comprises internally administering to the patient an effective amount of R-P88 , or a pharmaceutically acceptable salt thereof , or an ester of R-P88 or a pharmaceutically acceptable salt of such ester , once per day.2. The method of wherein the disorder is one that is amenable to treatment with iloperidone.3. The method of wherein the disorder is one or more of schizophrenia claim 1 , schizoaffective disorder claim 1 , bipolar disorder claim 1 , (mania and/or depression) claim 1 , depression claim 1 , major depression claim 1 , psychotic episodes claim 1 , autism claim 1 , autism spectrum disorder claim 1 , fragile X syndrome claim 1 , and pervasive developmental disorder.4. The method of claim 1 , wherein the R-P88 claim 1 , or the pharmaceutically acceptable salt thereof or the ester of R-P88 or the pharmaceutically acceptable salt of such ester claim 1 , is orally administered at a dose of 1 to 24 mg once per day.5. The method of claim 1 , wherein the R-P88 claim 1 , or the pharmaceutically acceptable salt thereof or the ester of R-P88 or the pharmaceutically acceptable salt of such ester claim 1 , is orally administered at a dose of 12 to 24 mg once per day.6. The method of claim 1 , wherein the R-P88 claim 1 , or the pharmaceutically acceptable salt thereof or the ester of R-P88 or the pharmaceutically acceptable salt of such ester claim 1 , is orally administered without titration.7. A method of treating a patient suffering from a psychiatric disorder that comprises internally administering to the patient an effective amount of R-P88 claim 1 , or a pharmaceutically acceptable salt thereof or an ester of R-P88 or a pharmaceutically acceptable salt of such ester claim 1 , twice per day.8. The method of claim 7 , wherein the disorder is one that is amenable to treatment with iloperidone.9. ...

Iloperidone for the treatment of schizophrenia

Aspects of the invention relate generally to the treatment of schizophrenia in an individual and, more specifically, to the treatment of an individual with iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof. In one embodiment, the invention provides a method of preventing schizophrenic relapse in an individual diagnosed with schizophrenia, the method comprising: administering to the individual iloperidone, an iloperidone metabolite, or a pharmaceutically-acceptable salt thereof at a daily dose between about 12 mg and about 16 mg following a period in which the individual's schizophrenia was stabilized.

METHODS OF TREATING SCHIZOPHRENIA

Provided herein are methods for determining if a compound has potential efficacy for the treatment for a specific symptom domain of schizophrenia, such as for example, the treatment of a negative symptom of schizophrenia. In addition, provided herein are methods of determining the prominent symptom domain of a subject suffering from schizophrenia. Further, provided herein are various methods for the treatment of the negative symptoms, cognitive dysfunction symptoms, or both, associated with schizophrenia comprising administering to a subject a therapeutically or prophylactically effective amount of various compounds. 181.-. (canceled)83. The method of wherein the neurological disorder is schizophrenia claim 82 , schizophrenia spectrum disorder claim 82 , acute schizophrenia claim 82 , chronic schizophrenia claim 82 , NOS schizophrenia claim 82 , schizoid personality disorder claim 82 , schizotypal personality disorder claim 82 , delusional disorder claim 82 , psychosis claim 82 , psychotic disorder claim 82 , brief psychotic disorder claim 82 , shared psychotic disorder claim 82 , psychotic disorder due to a general medical condition claim 82 , drug-induced psychosis claim 82 , psychoaffective disorder claim 82 , aggression claim 82 , delirium claim 82 , Parkinson's psychosis claim 82 , excitative psychosis claim 82 , Tourette's syndrome claim 82 , organic psychosis claim 82 , NOS psychosis claim 82 , seizure claim 82 , agitation claim 82 , post-traumatic stress disorder claim 82 , behavior disorder claim 82 , neurodegenerative disease claim 82 , Alzheimer's disease claim 82 , Parkinson's disease claim 82 , dyskinesias claim 82 , Huntington's disease claim 82 , dementia claim 82 , mood disorder claim 82 , anxiety claim 82 , affective disorder claim 82 , obsessive-compulsive disorder claim 82 , vertigo claim 82 , epilepsy claim 82 , pain claim 82 , fibromyalgia claim 82 , migraine claim 82 , cognitive impairment claim 82 , movement disorder claim 82 , restless leg ...

Composition and Method for Treating Metabolic Disorders

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects. 126.-. (canceled)27. A method for therapeutically modifying and resetting the central circadian rhythm of dopaminergic activity of a vertebrate , comprising administering to said vertebrate bromocriptine citrate.28. The method of which comprises administering bromocriptine citrate at a time of day that will increase central dopaminergic activity of the patient at the time of day the circadian peak of central dopaminergic activity in a healthy individual of the same species and sex.29. The method of which comprises administering bromocriptine citrate at a time of day that will increase central dopaminergic activity of the patient within four hours of the circadian peak of central dopaminergic activity in a healthy individual of the same species and sex.30. The method of wherein the resetting step comprises adjusting the central circadian rhythm of dopaminergic activity of a vertebrate to approximate the circadian peak dopaminergic activity of a healthy individual of the same species and sex.31. The method of wherein said bromocriptine ...

LOW DOSAGE SEROTONIN 5-HT2A RECEPTOR AGONIST TO SUPPRESS INFLAMMATION

Activation of 5-HTreceptors using agonists at surprisingly low concentrations was shown to potently inhibit TNF-α-induced inflammation in multiple cell types. Significantly, proinflammatory markers were also inhibited by the agonist, (R)-DOI, even many hours after treatment with TNF-α. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. TNF-α and TNF-α receptor mediated inflammatory pathways have been strongly implicated in a number of diseases, including atherosclerosis, asthma, rheumatoid arthritis, psoriasis, type II diabetes, depression, schizophrenia, and Alzheimer's disease. Importantly, because (R)-DOI can significantly inhibit the effects of TNF-α many hours after the administration of TNF-α, potential therapies could be aimed not only at preventing inflammation, but also treating inflammatory injury that has already occurred or is ongoing. 1. A method for the treatment of an inflammatory disorder in a mammal , said method comprising administering to a mammal in need of such treatment an therapeutically effective amount of a 5-HTreceptor agonist in an amount no greater than that required to result in a body fluid concentration no greater than 5 nM in a pharmaceutically acceptable carrier.2. The method of claim 1 , wherein the 5-HTreceptor agonist is selected from the group consisting of DOI claim 1 , (R)-1-(2 claim 1 ,5-dimethoxy-4-iodophenyl)-2-aminopropane ((R)-DOI) claim 1 , (4-Bromo-3 claim 1 ,6 dimethoxybenzocyclobuten-1-yl) methylamine (2C-BCB) claim 1 , and (2′S claim 1 ,4′S)-(+)-9 claim 1 ,10-Didehydro-6-methylergoline-8β-(trans-2 claim 1 ,4-dimethylazetidide)(LA-SS-Az)3. The method of claim 1 , wherein the 5-HTreceptor agonist is (R)-1-(2 claim 1 ,5-dimethoxy-4-iodophenyl)-2-aminopropane ((R)-DOI).4. The method of claim 3 , wherein the ((R)-DOI) is administered in an amount in an amount no greater than that required to result in a body fluid ...

COMPOSITIONS AND METHODS COMPRISING A COMBINATION OF SEROTONERGIC DRUGS

This disclosure pertains to new compositions and methods comprising a first serotonergic drug and a second serotonergic drug. In one embodiment, the compositions disclosed herein are used for a method of regulating a neurotransmitter receptor, e.g., a serotonin receptor. In one embodiment, the compositions disclosed herein comprise purified compounds, e.g., a purified psilocybin derivative, a purified cannabinoid, a purified terpene, a purified tryptamine, purified LSD, and/or purified MDMA. 1. A composition comprising a combination of first serotonergic drug and a second serotonergic drug.2. The composition of claim 1 , wherein the first serotonergic drug is a psilocybin derivative.3. The composition of claim 1 , wherein the first serotonergic drug is chosen from 6-Allyl-N claim 1 ,N-diethyl-NL claim 1 , N claim 1 ,N-Dibutyl-T claim 1 , N claim 1 ,N-Diethyl-T claim 1 , N claim 1 ,N-Diisopropyl-T claim 1 , 5-Methyoxy-alpha-methyl-T claim 1 , N claim 1 ,N-Dimethyl-T claim 1 , 2 claim 1 ,alpha-Dimethyl-T claim 1 , alpha claim 1 ,N-Dimethyl-T claim 1 , N claim 1 ,N-Dipropyl-T claim 1 , N-Ethyl-N-isopropyl-T claim 1 , alpha-Ethyl-T claim 1 , 6 claim 1 ,N claim 1 ,N-Triethyl-NL claim 1 , 3 claim 1 ,4-Dihydro-7-methoxy-1-methyl-C claim 1 , 7-Methyoxy-1-methyl-C claim 1 , N claim 1 ,N-Dibutyl-4-hydroxy-T claim 1 , N claim 1 ,N-Diethyl-4-hydroxy-T claim 1 , N claim 1 ,N-Diisopropyl-4-hydroxy-T claim 1 , N claim 1 ,N-Dimethyl-4-hydroxy-T claim 1 , N claim 1 ,N-Dimethyl-5-hydroxy-T claim 1 , N claim 1 ,N-Dipropyl-4-hydroxy-T claim 1 , N-Ethyl-4-hydroxy-N-methyl-T claim 1 , 4-Hydroxy-N-isopropyl-N-methyl-T claim 1 , 4-Hydroxy-N-methyl-N-propyl-T claim 1 , 4-Hydroxy-N claim 1 ,N-tetramethylene-T Ibogaine claim 1 , N claim 1 ,N-Diethyl-L claim 1 , N-Butyl-N-methyl-T claim 1 , N claim 1 ,N-Diisopropyl-4 claim 1 ,5-methylenedioxy-T claim 1 , N claim 1 ,N-Diisopropyl-5 claim 1 ,6-methylenedioxy-T claim 1 , N claim 1 ,N-Dimethyl-4 claim 1 ,5-methylenedioxy-T claim 1 , N claim 1 ,N- ...

Composition and Method for Treating Metabolic Disorders

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects. 1. Bromocriptine citrate.2. A pharmaceutical dosage form comprising bromocriptine citrate.3. A pharmaceutical dosage form comprising bromocriptine citrate and pharmaceutically acceptable excipients.4. The pharmaceutical dosage form of comprising an oral dosage form.5. The pharmaceutical dosage form of further comprising a low moisture content filler claim 2 , a water-scavenging agent or a lubricant.6. The pharmaceutical dosage form of further comprising at least one excipient that affects the rate of bromocriptine citrate release from said dosage form.7. The pharmaceutical dosage form of further comprising a disintegrating agent.8. The pharmaceutical dosage form of further comprising at least one of cornstarch claim 2 , mannitol claim 2 , colloidal silicon dioxide or stearic acid.9. The pharmaceutical dosage form of comprising between about 0.05 μg and about 0.5 mg/kg of body weight of bromocriptine citrate.10. The pharmaceutical dosage form of further comprising citric acid.11. The pharmaceutical dosage form of further comprising ...

FLUOROERGOLINE DERIVATIVES AND USES THEREOF

Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alphaand/or the alphareceptors using the compounds and compositions disclosed herein. 1. A fluoroergoline derivative composition suitable for use in the treatment of a disease , condition , or disorder selected from the group consisting of migraine , amyotrophic lateral sclerosis (ALS) , Parkinson's disease , stress/anxiety , nausea , emesis , aggression , pain , neuropathic pain , sleeplessness , insomnia , restless leg syndrome and depression.3. The composition of claim 2 , wherein the fluoroergoline derivative is in the form of a pharmaceutically acceptable salt claim 2 , solvate claim 2 , ester or hydrate.4. The composition of claim 3 , wherein the fluoroergoline derivative is in the form of a solid.5. The composition of claim 4 , wherein the composition is suitable for buccal administration.6. The composition of claim 4 , wherein the fluoroergoline derivative is in the form of amorphous claim 4 , semi-crystalline or crystalline particles.7. The composition of claim 6 , wherein the amorphous claim 6 , semi-crystalline or crystalline particles are suitable for administration via inhalation.8. The composition of claim 1 , wherein the composition comprises a pharmaceutically acceptable vehicle.9. The composition of claim 1 , wherein the composition comprises a pharmaceutically acceptable excipient.10. The composition ...

NOVEL SUBSTITUTED INDOLO 4,3 FG QUINOLINES USEFUL FOR TREATING MIGRAINE

Provided herein are novel ergoline derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand or 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein. 21. The method of claim 1 , wherein the compound of Formula (I) is formulated with a pharmaceutically acceptable vehicle.22. The method of claim 2 , wherein the compound of Formula (II) is formulated with a pharmaceutically acceptable vehicle. This application is a divisional of U.S. patent application Ser. No. 12/978,314, filed on Dec. 23, 2010, which claims priority under 35 U.S.C. §119 (e) from U.S. Provisional Application Ser. No. 61/289,987, filed Dec. 23, 2009, which are hereby incorporated by reference in their entirety.Provided herein are novel ergoline derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand or 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HTreceptor using ...

Pharmaceutical Formulation Containing Gelling Agent

Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient. 140-. (canceled)41. A therapeutic pharmaceutical composition comprising: a mixture including (a) an opioid; (b) a gel-forming polymer; (c) a disintegrant; and (d) a surfactant; wherein the pharmaceutical composition exhibits an immediate release profile.42. The therapeutic pharmaceutical composition of claim 41 , wherein the pharmaceutical composition is in unit dose form.43. The therapeutic pharmaceutical composition of claim 41 , wherein the pharmaceutical composition is in suppository claim 41 , capsule claim 41 , pill claim 41 , soft gelatin capsule claim 41 , or compressed tablet form.44. The therapeutic pharmaceutical composition of claim 41 , wherein the water soluble drug susceptible to abuse is present in an amount of 2.3 to 29.8 wt % of the composition.45. The therapeutic pharmaceutical composition of claim 41 , wherein the disintegrant is present in an amount of 5 to 15 wt % of the composition.46. The therapeutic pharmaceutical composition of claim 41 , wherein the surfactant is present in an amount of 1 to 10 wt % of the composition.47. The therapeutic pharmaceutical composition of claim 41 , wherein the gel-forming polymer is present in an amount of about 3 to about 40 wt % of the composition.48. The therapeutic pharmaceutical composition of claim 41 , wherein the disintegrant is selected from the ...

TREATMENT OF SCHIZOPHRENIA

The present invention relates to a method of treating schizophrenia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a selective D3 antagonist, wherein said subject has at least one negative symptom (NS) among the following core negative symptoms in PANSS: Blunted Affect (N1), Emotional Withdrawal (N2), Poor Rapport (N3), Passive withdrawal (N4), and Lack of Spontaneity (N6); with moderate or higher severity. Methods for improving the probability of success and/or the effect of a treatment of schizophrenia in a subject in need thereof are also described. 3. The method of claim 2 , wherein said pharmaceutically acceptable salt is N-(3-{4-[4-(8-oxo-8H-[1 claim 2 ,3]dioxolo[4 claim 2 ,5-g]chromen-7-yl)-butyl]-piperazin-1-yl}-phenyl)-methanesulfonamide hydrochloride.4. The method of claim 1 , wherein said subject suffers from acute exacerbation of schizophrenia before beginning of said treatment.5. The method of claim 4 , wherein said acute exacerbation is characterized by a PANSS total score ≥70 and ≥120.7. The method of claim 1 , wherein said therapeutically effective amount is a dose of 1 to 100 mg once daily or 0.5 to 50 mg twice daily.8. The method of claim 7 , wherein said therapeutically effective amount is a fixed dose of 40 mg once daily or 20 mg twice daily.9. The method of claim 7 , wherein said dose is administered orally.10. The method of claim 7 , wherein said dose is administered for 6 weeks or more to the subject in need thereof.13. The method of claim 12 , wherein said pharmaceutically acceptable salt is N-(3-{4-[4-(8-oxo-8H-[1 claim 12 ,3]dioxolo[4 claim 12 ,5-g]chromen-7-yl)-butyl]-piperazin-1-yl}-phenyl)-methanesulfonamide hydrochloride.14. The method of claim 11 , wherein said subject suffers from acute exacerbation of schizophrenia before beginning of said treatment.15. The method of claim 14 , wherein said acute exacerbation is characterized by a PANSS total score ≥70 and <120. ...

METHODS OF TREATING SCHIZOPHRENIA

Provided herein are methods for determining if a compound has potential efficacy for the treatment for a specific symptom domain of schizophrenia, such as for example, the treatment of a negative symptom of schizophrenia. In addition, provided herein are methods of determining the prominent symptom domain of a subject suffering from schizophrenia. Further, provided herein are various methods for the treatment of the negative symptoms, cognitive dysfunction symptoms, or both, associated with schizophrenia comprising administering to a subject a therapeutically or prophylactically effective amount of various compounds. 24.-. (canceled)6. The method of claim 5 , wherein m is 0; n is 1; Rand Rare each independently hydrogen claim 5 , optionally substituted C-Calkyl claim 5 , or optionally substituted C-Calkyl; Rand Rare each independently hydrogen or optionally substituted C-Calkyl; Ris hydrogen; and Rand Rare each independently hydrogen claim 5 , halo claim 5 , C-Calkyl claim 5 , aryl claim 5 , heteroaryl claim 5 , heterocyclyl claim 5 , alkoxyl claim 5 , or aminoalkyl claim 5 , each of which is optionally substituted.7. (canceled)8. The method of claim 5 , wherein Rand Rtogether with the nitrogen atom to which they are attached form a heteroaryl or heterocyclyl claim 5 , each of which is optionally substituted.9. (canceled)10. The method of claim 5 , wherein Rand Rtogether with the atoms to which they are attached form an optionally substituted heterocyclyl ring.11. (canceled)12. The method of claim 5 , wherein Rand Rtogether with the atom to which they are attached form a cycloalkyl or heterocyclyl ring claim 5 , which is optionally substituted.13. (canceled)14. The method of claim 5 , wherein Rand Rtogether with the atoms to which they are attached form an aryl or cycloalkyl ring claim 5 , which is optionally substituted.1533.-. (canceled)3560.-. (canceled)62. The method of claim 61 , wherein the method further comprises a step of determining if a subject exhibits ...

NOVEL NEUROMODULATORY COMPOUNDS

Provided herein are novel neuromodulatory compounds and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HTand/or the 5-HTreceptor, without agonizing the 5-HTreceptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alphaand/or the alphareceptors using the compounds and compositions disclosed herein. In other embodiments, provided herein are methods of agonizing dopaminergic Dreceptors and/or antagonizing or inhibiting activity of receptors such as the 5-HTreceptors using the compounds and compositions disclosed herein. 2. The compound of claim 1 , wherein Rand Rare not both —CHCH.3. A composition comprising the compound of and a vehicle.4. A method of treating a migraine in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound of .5. A method of treating a migraine in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the composition of .6. A method of treating one or more symptoms of Parkinson's disease in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound of .7. A method of treating one or more symptoms of Parkinson's disease in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the composition of .8. A method of agonizing the Dreceptor in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound of .9. A method of ...

PIMAVANSERIN FOR TREATING SCHIZOPHRENIA OR FOR TREATING PSYCHOSIS SECONDARY TO NEURODEGENERATIVE DISORDERS OR DEPRESSIVE DISORDER

The present disclosure relates generally to therapeutic use of pimavanserin or a pharmaceutical acceptable salt thereof. More specifically, the present disclosure provides methods for treating schizophrenia by administering pimavanserin or a pharmaceutical acceptable salt thereof as an adjunct therapy in a patient who has an inadequate response to another antipsychotic therapy. 1. A method of treating the loss of normal functions in a patient suffering from schizophrenia , wherein the patient has had a partial but inadequate response to an antipsychotic treatment , and is being administered the antipsychotic treatment , comprising orally administering once daily an effective amount of pimavanserin to the patient.2. The method of claim 1 , wherein the patient is not resistant to antipsychotic treatment.3. The method of or claim 1 , wherein the loss of normal function is a negative symptom of schizophrenia.4. The method of claim 3 , wherein the negative symptom is at least one of: emotional blunting claim 3 , emotional withdrawal claim 3 , poor rapport claim 3 , passive/apathetic social withdrawal claim 3 , difficulty in abstract thinking claim 3 , lack of spontaneity and flow of conversation claim 3 , and stereotyped thinking.5. The method of or claim 3 , wherein the loss of normal function is an aspect of sleep disturbance associated with schizophrenia.6. The method of any one of - wherein after 6 weeks of administering pimavanserin claim 3 , the patient improves on the negative syndrome subscale of PANSS compared to baseline.7. The method of any one of - claim 3 , wherein after 6 weeks of administering pimavanserin claim 3 , the patient improves on the PANSS Marder Negative factor score compared to baseline.8. The method of any one of - claim 3 , wherein after 6 weeks of administering pimavanserin claim 3 , the patient improves on the Karolinska Sleepiness Scale.9. A method of treating or diminishing a negative symptom of schizophrenia in a patient having a partial ...

THERAPEUTIC AGENT FOR MENTAL ILLNESS COMPRISING IL-6 INHIBITOR AS ACTIVE INGREDIENT

The present invention provides a novel therapeutic agent for mental illness. The therapeutic agent for mental illness comprises an IL-6 inhibitor as an active ingredient. 17-. (canceled)8. A method for treating or preventing mental illness in a subject , the method comprising the step of administering an effective amount of an interleukin 6 (IL-6) inhibitor to the subject having mental illness or the subject having the potential to develop mental illness.9. The method according to claim 8 , wherein the IL-6 inhibitor is an IL-6 receptor inhibitor.10. The method according to claim 8 , wherein the IL-6 inhibitor is an anti-IL-6 receptor antibody.11. The method according to claim 10 , wherein the anti-IL-6 receptor antibody is a chimeric antibody claim 10 , a humanized antibody claim 10 , or a human antibody.12. The method according to claim 8 , wherein the method suppresses the attenuation of a prepulse inhibitory effect.13. The method according to claim 8 , wherein the mental illness is schizophrenia claim 8 , Tourette syndrome claim 8 , and/or obsessive compulsive neurosis.14. The method according to claim 10 , wherein the anti-IL-6 receptor antibody is PM-1 antibody. The present invention relates to a therapeutic agent for mental illness. More specifically, the present invention relates to a therapeutic agent for mental illness comprising an interleukin 6 (IL-6) inhibitor as an active ingredient.Interleukin 6 (IL-6) is a cytokine also called B cell stimulatory factor 2 (BSF2) or interferon β2. IL-6 has been discovered as a differentiation factor involved in the activation of cells of B lymphocytic series (Non Patent Literature 1) and then found to be a multifunctional cytokine that influences the functions of various cells (Non Patent Literature 2). IL-6 has been reported to induce the maturation of cells of T lymphocytic series (Non Patent Literature 3).IL-6 transduces its biological activity via two proteins on cells. One of them is an IL-6 receptor which is a ...

METHODS OF TREATING NEUROLOGICAL AND PSYCHIATRIC DISORDERS

The present disclosure relates to methods of treating neurological or psychiatric diseases or disorders, such as schizophrenia. Compound 1, or a pharmaceutically acceptable salt thereof, is an antipsychotic agent with a non-D2 mechanism of action. Adverse events associated with antipsychotic agents that target the D2 dopamine receptor can be reduced by treating disorders with Compound 1, or a pharmaceutically acceptable salt thereof. 1. (canceled)4. (canceled)5. (canceled)7. A method of treating a neurological or psychiatric disease or disorder in a patient , comprising administering to the patient a therapeutically effective amount of an antipsychotic agent with no direct affinity to dopamine D2 receptors , wherein the method is substantially devoid of adverse events in the patient , wherein the adverse events are associated with antipsychotic agents with affinity to dopamine D2.10. The method of claim 2 , wherein the neurological or psychiatric disease or disorder is schizophrenia.11. The method of claim 2 , wherein the neurological or psychiatric disease or disorder is schizophrenia spectrum disorder claim 2 , schizophrenia negative symptoms claim 2 , attenuated psychosis syndrome claim 2 , prodromal schizophrenia claim 2 , delusional disorder claim 2 , psychosis claim 2 , psychotic disorder claim 2 , delirium claim 2 , Tourette's syndrome claim 2 , post-traumatic stress disorder claim 2 , behavior disorder claim 2 , affective disorder claim 2 , depression claim 2 , bipolar disorder claim 2 , major depressive disorder claim 2 , dysthymia claim 2 , manic disorder claim 2 , seasonal affective disorder claim 2 , obsessive-compulsive disorder claim 2 , narcolepsy claim 2 , REM behavior disorder claim 2 , substance abuse or dependency claim 2 , Lesch-Nyhan disease claim 2 , Wilson's disease claim 2 , autism claim 2 , Alzheimer's disease agitation and psychosis claim 2 , or Huntington's chorea.12. The method of claim 2 , wherein the neurological or psychiatric disease ...

COMPOSITIONS AND METHODS FOR TREATING NEGATIVE SYMPTOMS IN NON-SCHIZOPHRENIC PATIENTS

The present disclosure describes compositions and methods for treating at least one negative symptom in a human subject who does not have a clinical diagnosis of schizophrenia. The compositions and methods employ a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate or polymorph thereof. 110.-. (canceled)12. The method of claim 11 , wherein the total daily dose of Compound I is between about 10 mg to about 64 mg claim 11 , 20 mg to about 64 mg claim 11 , or about 30 mg to about 64 mg.13. The method of claim 11 , wherein the total daily dose of Compound I is 32 mg or 64 mg.14. The method of claim 11 , wherein the negative symptom is selected from the group consisting of: blunted affect claim 11 , alogia claim 11 , amotivation claim 11 , anhedonia and asociality.15. The method of claim 11 , wherein the negative symptom is selected from the group consisting of: blunted affect claim 11 , emotional withdrawal claim 11 , poor rapport claim 11 , passive/apathetic social withdrawal claim 11 , difficulty in abstract thinking claim 11 , lack of spontaneity and flow of conversation claim 11 , and stereotyped thinking.16. The method of claim 11 , wherein the non-schizophrenic patient is diagnosed with a mental disorder or a neurological condition.17. The method of claim 16 , wherein the mental disorder or neurological condition is selected from the group consisting of: dementia claim 16 , frontotemporal dementia (FTD) claim 16 , Alzheimer's disease claim 16 , autism spectrum disorder (ASD) claim 16 , bipolar disorder (BPD) claim 16 , major depressive disorder (MDD) claim 16 , Parkinson's disease claim 16 , temporal lobe epilepsy claim 16 , post-cerebrovascular accident (CVA) claim 16 , traumatic brain injury (TBI) claim 16 , post brain trauma syndrome claim 16 , mild to moderate mental retardation claim 16 , viral encephalitis claim 16 , and drug addiction.18. The method of claim 17 , wherein the mental disorder ...

PROCESS OF SYNTHESIZING 2-BROMO-LSD

A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with a brominating agent to produce [(15)-1-(Hydroxymethyl)propylamino][(6aR, 9R)-5 -bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde as a first intermediate, and then hydrolyzing [(15)-1-(Hydroxymethyl)propylamino][(6aR,9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde to yield bromo-lysergic acid as a second intermediate, wherein bromo-lysergic acid is then amidated to yield 2-bromo-LSD or a salt or hydrate thereof. 1. A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with N-bromosuccinimide to produce [(1S)-1-(Hydroxymethyl)propylamino][(6aR, 9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde as a first intermediate, and then reacting [(1S)-1-(Hydroxymethyl)propylamino][(6aR,9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde with a strong base to yield bromo-lysergic acid as a second intermediate, wherein bromo-lysergic acid is then reacted with an acylating agent in the presence of an amine to yield 2-bromo-LSD or a salt or hydrate thereof. The present application claims the benefit of the filing date of U.S. Provisional Patent Application 62/101,278, filed Jan. 8, 2015, the disclosure of which is hereby incorporated by reference herein in its entirety.The synthesis of BOL-148 in the United States and many other countries is plagued with a handful of regulatory and chemistry issues. The first synthesis of 2-Bromo-LSD (BOL-148) comprised reacting 13.2 grams of N-bromosuccinimide (in 400 mL dioxane) with 1.2 liters of dioxane containing 25 grams of LSD. This gave 11 grams of crude product, which had to be recrystallized. The radioactive synthesis uses effectively elemental bromine, and provided yields ranging from 5 to 15%.LSD is a ...

ISOERGOLINE COMPOUNDS AND USES THEREOF

Provided herein are isoergoline compounds and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT, 5-HTand 5-HTreceptors without agonizing the 5-HTreceptor using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HTadrenergic alphaand/or the alphareceptors using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the D2 and D3 receptor using the compounds and pharmaceutical compositions disclosed herein. 124-. (canceled)26. The compound of claim 25 , wherein Ris methyl.27. The compound of claim 26 , wherein Rand R claim 26 , together with the atoms to which they are joined form a double bond.28. The compound of claim 27 , wherein Ris hydrogen claim 27 , CF claim 27 , Br claim 27 , or cyclopropyl.29. The compound of claim 28 , wherein Ris hydrogen.30. The compound of claim 28 , wherein Ris CF.31. The compound of claim 28 , wherein Ris Br.32. The compound of claim 28 , wherein Ris cyclopropyl.33. The compound of claims 29 , wherein Ris methyl claims 29 , b is 1 claims 29 , and Ris hydrogen.34. The compound of claim 30 , wherein Ris methyl claim 30 , b is 1 claim 30 , and Ris hydrogen.35. The compound of claim 31 , wherein Ris methyl claim 31 , b is 1 claim 31 , and Ris hydrogen.36. The compound of claim 32 , wherein Ris methyl claim 32 , b is 1 claim 32 , and Ris hydrogen.37. The compound of claim 29 , wherein Ris CHCF claim 29 , b is 1 claim 29 , and Ris hydrogen.38. The compound of claims 29 , wherein Ris CF claims 29 , b is 1 claims 29 , and Ris hydrogen.39. The compound of ...

8'-HYDROXY-DIHYDROERGOTAMINE COMPOUNDS AND COMPOSITIONS

8′-Hydroxy-Dihydroergotamine (8′-OH DHE) medicinal compounds, compositions, and dosage forms containing such compositions are provided. Also provided herein are methods of treatment, prevention, or amelioration of migraine disorders using the compounds, compositions, dosage forms and administration techniques disclosed herein. 2. The method of claim 1 , wherein said treatment comprises a reduction in one or more migraine symptoms.3. The method of claim 1 , wherein said treatment comprises partial relief from at least one migraine symptom.4. The method of claim 3 , wherein said treatment further comprises sustained relief from the at least one migraine symptom.5. The method of claim 2 , wherein said treatment is further characterized by not inducing one or more drug-induced side-effects.6. The method of claim 5 , wherein said one or more drug-induced side-effect is selected from nausea claim 5 , emesis claim 5 , chest tightness and cardiovascular effects.7. The method of claim 1 , wherein said 8′-OH DHE is administered at a rate sufficient to provide a maximum circulating plasma level (C) of 8′-OH DHE that is less than 500 pg/mL.8. The method of claim 1 , wherein said 8′-OH DHE is administered at a rate sufficient to provide a maximum circulating plasma level (C) of 8′-OH DHE that is less than 2 claim 1 ,500 pg/mL.9. The method of claim 1 , wherein said 8′-OH DHE is administered at a rate sufficient to provide a maximum circulating plasma level (C) of 8′-OH DHE that is less than 5 claim 1 ,000 pg/mL.10. The method of claim 1 , wherein said 8′-OH DHE is administered in the form of a solution claim 1 , suspension claim 1 , tablet claim 1 , dispersible tablet claim 1 , pill claim 1 , capsule claim 1 , powder claim 1 , sustained release composition claim 1 , an elixir claim 1 , a sterile solution or suspension suitable for parenteral administration claim 1 , a topical dosage form claim 1 , a transdermal dosage form claim 1 , a nasal dosage form claim 1 , or a pulmonary ...

METHOD FOR PREDICTING A SUBJECT'S RESPONSE TO VALPROIC ACID THERAPY

The present invention provides, inter alia, methods for treating or ameliorating the effects of a disorder, such as schizophrenia or bipolar disorder, by increasing or decreasing proline levels. Further provided are methods of predicting and monitoring the clinical response in a patient, and diagnostic systems for identifying a patient likely to benefit from proline modulation. 1. A method for predicting the clinical response of a subject with a disorder to a proline modulator comprising:a) obtaining a biological sample from the subject;{'sup': '158', 'b) determining the identity of the allele(s) of the ValMet locus associated with the COMT gene in the sample;'}wherein the presence of Val/Val is indicative of a subject who will benefit from an agent that increases proline levels, and wherein the presence of at least one Met allele is indicative of a subject who will benefit from an agent that decreases proline levels; andc) administering, if appropriate based on the results of step b), an effective amount of a proline modulator to the subject to achieve an appropriate clinical response.2. The method of claim 1 , further comprising determining a proline level in the subject and adjusting a treatment protocol for the subject based on the determined proline level.3. The method of claim 1 , wherein the disorder is a psychiatric disorder.4. The method of claim 1 , wherein the disorder is selected from the group consisting of schizophrenia claim 1 , bipolar disorder claim 1 , schizophrenia spectrum and other psychotic disorders claim 1 , 22q11.2 deletion syndrome claim 1 , depressive disorders claim 1 , mood disorders claim 1 , Alzheimer's disease claim 1 , substance use disorders claim 1 , addictive disorders claim 1 , alcohol use disorder (AUD) claim 1 , anxiety disorders claim 1 , obsessive-compulsive disorders claim 1 , traumatic brain injury (TBI) claim 1 , and trauma and stressor-related disorders.5. The method of claim 4 , wherein the disorder is schizophrenia.6. ...

ANTIBODY-DRUG CONJUGATE

As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula: -L-L-L-NH—(CH)n-L-L-L- wherein the antibody is connected to the terminal of L, and the antitumor compound is connected to the terminal of Lwith the nitrogen atom of the amino group at position 1 as a connecting position. 2. The antibody-drug conjugate according to claim 1 , wherein the anti-B7-H3 antibody has a heavy chain variable region and a light chain variable region selected from the group consisting ofa heavy chain variable region comprising an amino acid sequence described in amino acid positions 20 to 141 in SEQ ID NO: 9 and a light chain variable region comprising an amino acid sequence described in amino acid positions 21 to 128 in SEQ ID NO: 13,a heavy chain variable region comprising an amino acid sequence described in amino acid positions 20 to 141 in SEQ ID NO: 9 and a light chain variable region comprising an amino acid sequence described in amino acid positions 21 to 128 in SEQ ID NO: 14,a heavy chain variable region comprising an amino acid sequence described in amino acid positions 20 to 141 in SEQ ID NO: 9 and a light chain variable region comprising an amino acid sequence described in amino acid positions 21 to 128 in SEQ ID NO: 15,a heavy chain variable region comprising an amino acid sequence described in amino acid positions 20 to 141 in SEQ ID NO: 9 and a light chain variable region comprising an amino acid sequence described in amino acid positions 21 to 128 in SEQ ID NO: 16,a heavy chain variable region comprising an amino acid sequence described in amino acid positions 20 to 141 in SEQ ID NO: 9 and a light chain variable region comprising an amino acid sequence described in amino acid positions 21 to 128 in SEQ ID NO: 17,a heavy chain variable region ...

ERGOLINE DERIVATIVES AS DOPAMINE RECEPTOR MODULATORS

The invention provides compounds of formula (I) wherein R-Rhave any of the values defined in the specification, and salts thereof. The compounds are useful as dopamine receptor modulators for the treatment of diseases where modulation of dopamine receptors is implicated (e.g. sexual dysfunction, prolactinoma, Parkinson's disease, and Cushings disease). 3. The compound of wherein Ris —C(═O)NRR.4. The compound of wherein Ris —C(═O)OR.5. The compound of wherein Ris (C-C)alkyl claim 1 , (C-C)alkanoyl claim 1 , (C-C)alkoxycarbonyl claim 1 , or (C-C)alkanoyloxy claim 1 , wherein any (C-C)alkyl claim 1 , (C-C)alkanoyl claim 1 , (C-C)alkoxycarbonyl claim 1 , or (C-C)alkanoyloxy can optionally be substituted with one or more halo claim 1 , hydroxy claim 1 , (C-C)alkoxy claim 1 , (C-C)alkanoyl claim 1 , (C-C)alkoxycarbonyl claim 1 , (C-C)alkanoyloxy claim 1 , or NRR.6. The compound of wherein Ris (C-C)alkyl claim 1 , optionally substituted with one or more (C-C)alkoxy.7. The compound of wherein Ris dimethoxymethyl.8. The compound of wherein Ris N-(3-dimethylaminopropyl)aminocarbonyl.11. The compound of wherein Ris H.12. The compound of wherein Ris (C-C)alkyl.13. The compound of wherein Ris methyl.14. A pharmaceutical composition comprising a compound as described in and a pharmaceutically acceptable diluent or carrier.15. A method for treating sexual dysfunction claim 1 , prolactinoma claim 1 , Parkinson's disease claim 1 , depression claim 1 , restless leg syndrome claim 1 , or Cushings disease in an animal comprising administering a compound of formula I or a pharmaceutically acceptable salt thereof as described in to the animal.1618-. (canceled)19. A method for modulating the activity of a dopamine receptor in an animal comprising administering a compound of formula I or a pharmaceutically acceptable salt thereof as described in to the animal.2021-. (canceled) This application claims priority to U.S. Provisional Application No. 61/728,121 that was filed on Nov. 19, 2012. ...

Composition and Method for Treating Metabolic Disorders

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects. 1. Bromocriptine citrate.2. A pharmaceutical dosage form comprising bromocriptine citrate.3. A pharmaceutical dosage form comprising bromocriptine citrate and pharmaceutically acceptable excipients.4. The pharmaceutical dosage form of comprising an oral dosage form.5. The pharmaceutical dosage form of further comprising a low moisture content filler claim 2 , a water-scavenging agent or a lubricant.6. The pharmaceutical dosage form of further comprising at least one excipient that affects the rate of bromocriptine citrate release from said dosage form.7. The pharmaceutical dosage form of further comprising a disintegrating agent.8. The pharmaceutical dosage form of further comprising at least one of cornstarch claim 2 , mannitol claim 2 , colloidal silicon dioxide or stearic acid.9. The pharmaceutical dosage form of comprising between about 0.05 μg and about 0.5 mg/kg of body weight of bromocriptine citrate.10. The pharmaceutical dosage form of further comprising citric acid.11. The pharmaceutical dosage form of further comprising ...

Aripiprazole Dosing Strategy

The present invention relates to methods of treating schizophrenia using a combination of aripiprazole, aripiprazole lauroxil, and a nanoparticle dispersion of aripiprazole lauroxil. 1. A method of treating schizophrenia in a subject in need thereof , the method comprising administering to the subject:a first component comprising about 5-50 mg of aripiprazole;{'sub': 'NCD', 'a second component comprising about 629-695 mg of AL; and'}a third component comprising a therapeutically effective amount of aripiprazole lauroxil.2. The method of claim 1 , wherein the ALcomprises polysorbate 20 claim 1 , sodium citrate claim 1 , sodium chloride claim 1 , an aqueous buffer claim 1 , and a population of particles of aripiprazole lauroxil.3. The method of claim 2 , wherein the population of particles of aripiprazole lauroxil has a volume-based particle distribution size (Dv50) between about 175 nm and about 350 nm.4. The method of claim 2 , wherein the ALhas a ratio of particles to polysorbate 20 of 17:1.5. The method of claim 1 , wherein the first component is administered at a dosage of about 30 mg or about 15 mq.6. (canceled)7. The method of claim 1 , wherein the second component is administered at a dosage of about 675 mg of the active component.8. The method of claim 1 , wherein the third component is administered at a dosage of about 300-1500 mg.9. The method of claim 1 , wherein the third component is administered at a dosage of 441 claim 1 , 662 claim 1 , 882 claim 1 , or 1064 mg.10. The method of claim 1 , wherein all components of the method are administered at substantially the same time.11. The method of claim 1 , wherein the method comprises a regimen wherein the first claim 1 , second claim 1 , and third components are administered at substantially the same time claim 1 , and wherein the first component is not administered again within 21 days of the initial administration.12. (canceled)13. The method of claim 1 , wherein the method comprises a regimen wherein the ...

ASTROCYTE DIFFERENTIATION PROTOCOL

The disclosure provides for methods of compositions for making astrocytes from induced pluripotent stem cells as well as method of treating and diagnosing neurological disorders such as Rett syndrome. 1. A cell culture method of generating astrocytes comprising:culturing neuronal precursor cells (NPCs) to confluence in media contain neuronal growth factor (NGF);washing and incubating the NPCs with dPBS;scraping the NPCs to form neurospheres in media containing NGF;dissociating, plating and culturing the neurospheres under shaking conditions until neurospheres are well formed;adding ROCK inhibitor in FGF-free NGF containing media and culturing for 1 to 3 days;passaging and culturing the neurospheres in FGF-free NGF media without ROCK inhibitor for about 1 week;subculturing the neurospheres in astrocyte media for about 2 weeks with shaking; andisolating astrocytes that project outside of the spheres to populate the culture plate.2. The method of claim 1 , wherein the NPCs are obtained from induced pluripotent stem cells.3. The method of claim 1 , wherein the induced pluripotent stem cells are obtained from fibroblasts.4. The method of claim 3 , wherein the fibroblasts are obtained from a subject having a neuronal disease claim 3 , disorder or syndrome.5. The method of claim 4 , wherein the neuronal disease claim 4 , disorder or syndrome is selected from the group consisting of autism claim 4 , RETT syndrome claim 4 , schizophrenia claim 4 , Fragile X syndrome claim 4 , Angelman syndrome and Timothy syndrome.6. The method of claim 2 , wherein in the induced pluripotent stem cells are cultured to obtain embryoid bodies and wherein the embryoid bodies are cultured with dual SMAD inhibitors to obtain NPCs.7. The method of claim 5 , wherein the dual SMAD inhibitors comprise Noggin and SB431542.8. The method of claim 1 , wherein the media containing NGF comprises DMEM/F12 media supplemented with 0.5×N2 claim 1 , 0.5× Gem21 supplement claim 1 , 20 ng/mL of FGF and 1% ...

USE OF CARBAMATE COMPOUNDS FOR PREVENTION, ALLEVIATION OR TREATMENT OF BIPOLAR DISORDER

The present invention relates to a use for the purpose of preventing, alleviating, or treating bipolar disorder by administering a pharmaceutical composition comprising a carbamate compound of the following chemical formula 1. 114-. (canceled)16. The method according to claim 15 , wherein Rand Rare each independently selected from the group consisting of hydrogen claim 15 , halogen and C-Calkyl.18. The method according to claim 15 , wherein the method is for the prevention claim 15 , alleviation or treatment of mania of bipolar disorder.19. The method according to claim 15 , wherein the bipolar disorder is one or more selected from the group consisting of bipolar disorder Type I claim 15 , bipolar disorder Type II claim 15 , cyclothymic disorder and bipolar disorder not otherwise classified.20. The method according to claim 15 , wherein the subject is a mammal.21. The method according to claim 20 , wherein the mammal is a human.22. The method according to claim 15 , wherein the therapeutically effective amount of the carbamate compound of Formula 1 is 50 mg to 500 mg based on the free form.2328-. (canceled) The present invention relates to use of a carbamate compound of the following Formula 1 for the purpose of preventing, alleviating or treating bipolar disorder by administering a pharmaceutical composition comprising said carbamate compound:wherein,R, R, Aand Aare as defined herein.Bipolar disorder (BPD) is a mood disorder that is accompanied by mania and depression, which is a chronic, cyclic psychiatric disorder. According to DSM-IV, bipolar disorder is classified as bipolar disorder Type I, bipolar disorder Type II, cyclothymic disorder, and bipolar disorder not otherwise classified. When a patient has experienced more than one manic episode or a mixed episode in which depressive episodes and manic episodes occur simultaneously, he/she is diagnosed as bipolar disorder Type I. Bipolar disorder Type II refers to a case in which a patient having a medical history ...

METHODS OF TREATING BEHAVIOR ALTERATIONS

Provided herein are methods for treating behavior alterations using KDM1A inhibitors, particularly 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine. 1. A KDM1A inhibitor for use in the treatment of a behavior alteration.2. A pharmaceutical composition for use in the treatment of a behavior alteration , wherein the pharmaceutical composition comprises a KDM1A inhibitor and one or more pharmaceutically acceptable excipients or carriers.3. The compound for use according to or the pharmaceutical composition for use according to , wherein the behavior alteration is a social behavior alteration.4. The compound for use according to or or the pharmaceutical composition for use according to or , wherein the behavior alteration is social withdrawal.5. The compound for use according to or or the pharmaceutical composition for use according to or , wherein the behavior alteration is aggressiveness.6. The compound for use according to any one of or to or the pharmaceutical composition for use according to any one of to , wherein the patient to be treated is a human.7. The compound for use according to any one of or to or the pharmaceutical composition for use according to any one of to , wherein the KDM1A inhibitor is 5-((((1R ,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1 ,3 ,4-oxadiazol-2-amine , or a pharmaceutically acceptable salt or solvate thereof.8. The compound for use according to any one of or to or the pharmaceutical composition for use according to any one of to , wherein the KDM1A inhibitor or the pharmaceutical composition is administered orally.9. A method for treating a behavior alteration in a patient , comprising administering to the patient a therapeutically effective amount of a KDM1A inhibitor.10. The method according to claim 9 , wherein the behavior alteration is a social behavior alteration.11. The method according to or claim 9 , wherein the behavior alteration is social withdrawal.12. The method according ...

PROCESS OF SYNTHESIZING 2-BROMO-LSD

A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with a brominating agent to produce [(1S)-1-(Hydroxymethyl)propylamino][(6aR,9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde as a first intermediate, and then hydrolyzing [(1S)-1-(Hydroxymethyl)propylamino][(6aR, 9R)-5-bromo-7-methyl-4,7-diaza-4,6,6a,7,8,9-hexahydroacephenanthrylen-9-yl]formaldehyde to yield bromo-lysergic acid as a second intermediate, wherein bromo-lysergic acid is then amidated to yield 2-bromo-LSD or a salt or hydrate thereof. 1. A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the steps of reacting methylergometrine with N-bromosuccinimide to produce [(1S)-1-(Hydroxymethyl)propylamino][(6aR ,9R)-5-bromo-7-methyl-4 ,7-diaza-4 ,6 ,6a ,7 ,8 ,9-hexahydroacephenanthrylen-9-yl]formaldehyde , and then reacting [(1S)-1-(Hydroxymethyl)propylamino][(6aR ,9R)-5-bromo-7-methyl-4 ,7-diaza-4 ,6 ,6a ,7 ,8 ,9-hexahydroacephenanthrylen-9-yl]formaldehyde with a strong base to yield bromo-lysergic acid , wherein bromo-lysergic acid is then reacted with an acylating agent in the presence of an amine to yield 2-bromo-LSD or a salt or hydrate thereof.2. The method of claim 1 , wherein the amine is diethylamine.3. The method of claim 1 , wherein the amine is dimethylamine.4. The method of claim 1 , wherein bromo-lysergic acid is reacted with POCland diethylamine.5. The method of claim 4 , wherein a ratio of an amount of POClto an amount of bromo-lysergic acid ranges from about 1:1 to about 1:3.6. The method of claim 1 , wherein the strong base is KOH.7. A process of synthesizing 2-bromo-LSD or a salt or hydrate thereof comprising the step of reacting bromo-lysergic acid with POCl claim 1 , wherein a ratio of an amount of POClto an amount of bromo-lysergic acid ranges from about 1:1 to about 1:3. The present application claims the benefit of the filing date of U.S. Provisional Patent ...

IDENTIFICATION OF AGENTS DISPLAYING FUNCTIONAL ACTIVATION OF DOPAMINE D2 AND D4 RECEPTORS

A method of treating psychosis, and the underlying antipsychotic formulation. The method includes administering a therapeutically effective amount of synthetic agents that selectively recruit β-arrestin to D2 receptors and have little-to-no binding to culprit receptors associated with weight gain and Type II diabetes. The synthetic agents can include SYA16263 and SYA16264, and/or derivatives or analogs thereof. The 1-(pyridin-2-yl)piperazine moiety was found to play a significant role in recruiting β-arrestin to D2 receptors. In other embodiments, the current invention relates to synthetic agents that are selective of D4 receptors for treatment of psychosis and erectile dysfunction. The synthetic agents can include SYA27287 and/or derivatives or analogs thereof. In all embodiments, extrapyramidal side effects are eliminated or minimized. 1. A method of treating psychosis in a subject , comprising the step of administering a therapeutically effective amount of a synthetic agent in a pharmaceutically effective carrier , wherein the synthetic agent selectively recruits β-arrestin to D2 dopamine receptors , such that the subject is substantially free of extrapyramidal symptoms upon administration of the synthetic agent , wherein the therapeutically effective amount of the synthetic agent is at least 1 mg/kg of the subject , wherein the synthetic agent is selected from the group consisting of: SYA16263 , SYA16264 , and analogs thereof , and wherein the synthetic agent includes a 1-(pyridine-2-yl)piperazine moiety or a 2-(piperazine-1-yl)pyrimidine moiety.2. A method as in claim 1 , wherein the therapeutically effective amount is at least about 50 mg/kg of the subject.3. A method as in claim 1 , wherein the psychosis is schizophrenia.4. A method of reversing cognitive deficits associated with a mental disorder suffered by a subject claim 1 , the mental disorder being psychosis claim 1 , the method comprising the step of administering a therapeutically effective amount of ...

Method for preparing ergolin derivatives

The novel ergoline derivatives of the general formula I …<CHEM>… wherein R1 represents an ally or alkoxy group having from 1 to 4 carbon atoms, phenyl, a 5- or 6-membered heterocyclic ring which is preferably saturated, an amino group, a substituted amino group of the formula NHR min (wherein R min represents an alkyl group having from 1 to 4 carbona toms, a cycloalkyl group, a benzyl group or a phenyl group), or a substituted amino group of the formula NR sec R''' (wherein R sec and R''' both represent alkyl groups having from 1 to 4 carbon atoms);… R2 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms or a phenyl group;… R3 represents a halogen atom, a cyano group, a halogenated lower alkyl group, methylthio, methylsulfonyl or sulfonamido group, an alkoxy group having from 1 to 4 carbon atoms, an acyl group, having from 2 to 5 carbon atoms or a benzoyl group;… R4 represents a hydrocarbon group having from 1 to 4 carbon atoms;… R<5> represents a hydrogen atom or a methoxy group;… R6 is hydrogen, a halogen atom or a methyl group;… R7 is hydrogen or a methyl group;… and the pharmaceutically acceptable addition salts with organic or inorganic acids thereof exhibit antihypertensive and antiprolactinic activity. Their preparation is described, e.g. 2-cyano3- (6 min -methyl-ergoline-8 min beta )-propionic acid ethyl ester is obtained by reacting sodium ethyl cyanoacetate with 6-methyl-8 beta -tosyloxymethylergoline.

METHOD FOR PRODUCING ERGOLIN DERIVATIVES

Способ получени производных /эрголинил/-N,N-диэтилмочевины или их солей

麦角灵衍生物的制备方法

本发明提供了一种制备式I的麦角灵衍生物的 方法，该方法是在金属催化剂和磷化合物存在下使式 II的麦角灵酰胺与式III的异氰酸酯反应，式I的化合 物是有用的抗促乳素和抗帕金森氏病的药物。

Method of obtaining d-2-halogen-6-methyl-8-cyanomethyl- or d-2-halogen-6-methyl-8-carboxamidomethylergolines

Method of preparing 6-methyl-8-substituted-methylergolines or their salts

Method of preparing d-2-substituted-6-methyl-8-cyanomethyl-8-cyanomethylergolines or salts thereof

Method of producing ergolines or physiologically acceptable salts thereof

A process for preparing an ergoline of the formula wherein C s = C 10 is a CC single or double bond, R' is a hydrogen or CONR 2 , R being hydrogen, methyl, or ethyl, and wherein NR' is in the a- or β-position, R 2 is lower alkyl of up to 3 carbon atoms, and the salts thereof, comprises treating the corresponding ergolinyl carboxylic acid amide with lead (IV) acetate in an aprotic polar solvent; reacting the intermediarily formed corresponding isocyanate with water or with a reactive amine of up to 4 carbon atoms, (e.g. a mono- or dialkylamine of up to 4-C atoms); and, optionally, treating the resultant product with an acid to form the corresponding salt.

Method for producing lysergic acid amides or their salts

Patent JPS5813541B2

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AGENT FOR TREATMENT OF SCHIZOPHRENIA ON BASIS OF HYDROGENATED PYDIDO (4,3-b) INDOLES (VERSIONS), PHARMACOLOGICAL AGENT ON ITS BASIS AND METHOD OF ITS APPLICATION

FIELD: medicine; pharmacology. SUBSTANCE: invention concerns application of hydrogenated pyrido (4,3-b) indoles of the formula (1) as an agent for schizophrenia treatment. The pharmacological agent on the basis of hydrogenated pyrido (4,3-b) indoles of the formula (1) and the method of treatment of the schizophrenia, consisting in introduction of the offered pharmacological agent is also revealed. EFFECT: expansion of an arsenal of agents for schizophrenia treatment. 11 cl, 2 tbl, 2 ex ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (11) 2 338 537 (13) C2 (51) ÌÏÊ A61K A61K A61K A61P 31/4427 (2006.01) 31/407 (2006.01) 31/404 (2006.01) 25/18 (2006.01) ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÎÏÈÑÀÍÈÅ ÈÇÎÁÐÅÒÅÍÈß Ê ÏÀÒÅÍÒÓ (21), (22) Çà âêà: 2006101999/15, 25.01.2006 (72) Àâòîð(û): Áà÷óðèí Ñåðãåé Îëåãîâè÷ (RU), Ãðèãîðüåâ Âëàäèìèð Âèêòîðîâè÷ (RU), Ìîðîçîâà Ìàðãàðèòà Àëåêñååâíà (RU), Áåíèàøâèëè Àëëàí Ãåðîâè÷ (RU) (24) Äàòà íà÷àëà îòñ÷åòà ñðîêà äåéñòâè ïàòåíòà: 25.01.2006 (43) Äàòà ïóáëèêàöèè çà âêè: 10.08.2007 (54) ÑÐÅÄÑÒÂÎ ÄËß ËÅ×ÅÍÈß ØÈÇÎÔÐÅÍÈÈ ÍÀ ÎÑÍÎÂÅ ÃÈÄÐÈÐÎÂÀÍÍÛÕ ÏÈÐÈÄÎ(4,3- b)ÈÍÄÎËΠ(ÂÀÐÈÀÍÒÛ), ÔÀÐÌÀÊÎËÎÃÈ×ÅÑÊÎÅ ÑÐÅÄÑÒÂÎ ÍÀ ÅÃÎ ÎÑÍÎÂÅ È ÑÏÎÑÎÁ ÅÃÎ ÏÐÈÌÅÍÅÍÈß (57) Ðåôåðàò: Èçîáðåòåíèå îòíîñèòñ ê ëåêàðñòâåííûì ñðåäñòâàì è êàñàåòñ ïðèìåíåíè ãèäðèðîâàííûõ ïèðèäî(4,3-b)èíäîëîâ ôîðìóëû (1) â êà÷åñòâå ñðåäñòâà äë ëå÷åíè øèçîôðåíèè. Òàêæå ðàñêðûâàåòñ ôàðìàêîëîãè÷åñêîå ñðåäñòâî íà îñíîâå ãèäðèðîâàííûõ ïèðèäî (4,3-b) èíäîëîâ ôîðìóëû (1) è ñïîñîá ëå÷åíè øèçîôðåíèè, çàêëþ÷àþùèéñ âî ââåäåíèè ïðåäëîæåííîãî ôàðìàêîëîãè÷åñêîãî ñðåäñòâà. Èçîáðåòåíèå ïîçâîë åò ðàñøèðèòü àðñåíàë ñðåäñòâ äë ëå÷åíè øèçîôðåíèè. 3 í. è 8 ç.ï. ô-ëû, 2 òàáë. C 2 R U 2 3 3 8 5 3 7 C 2 Àäðåñ äë ïåðåïèñêè: 142432, Ìîñêîâñêà îáë., Íîãèíñêèé ð-í, ã. ×åðíîãîëîâêà, Øêîëüíûé á-ð, 19, êâ.94, Â.Â. Ãðèãîðüåâó Ñòðàíèöà: 1 RU 2 3 3 8 5 3 7 (56) Ñïèñîê äîêóìåíòîâ, öèòèðîâàííûõ â îò÷åòå î ïîèñêå: RU 2067980 Ñ1, 20.10.1996. RU 2081117 C1, 10.06.1997. RU 2106864 C1, 20.03.1998. WO 2006061428 ...

The method of obtaining derivatives of ergolene or ergolin

METHOD FOR PRODUCING LYSERGINIC ACID

1. Способ получения лизергиновой кислоты, включающий изомеризацию паспаловой кислоты в смеси с разделенными фазами, содержащей паспаловую кислоту и водный раствор гидроксида металла.2. Способ по п.1, где гидроксид металла выбран из гидроксида натрия и гидроксида калия.3. Способ по п.2где смесь с разделенными фазами содержит по меньшей мере около 5% по массе паспаловой кислоты.4. Способ по п.3, где водный раствор гидроксида натрия или гидроксида калия содержит по меньшей мере около 12% по массе гидроксида натрия или гидроксида калия, растворенного в воде.5. Способ по п.3, где изомеризацию осуществляют при температуре в пределах около 40-60°C.6. Способ по п.2, дополнительно включающий подкисление реакционной смеси после изомеризации для образования кристаллической соли лизергиновой кислоты.7. Способ по п.6, где реакционную смесь подкисляют до значения pH около 4 или меньше.8. Способ по п.6, где для подкисления реакционной смеси используют серную кислоту.9. Способ по п.6, дополнительно включающий выделение соли лизергиновой кислоты.10. Способ по п.9, дополнительно включающий экстракцию лизергиновой кислоты из выделенной соли лизергиновой кислоты смесью спирта и водного раствора аммиака с образованием раствора лизергиновой кислоты.11. Способ по п.10, где спиртом является метанол.12. Способ по п.11, дополнительно включающий уменьшение объема раствора лизергиновой кислоты.13. Способ по п.12, дополнительно включающий кристаллизацию лизергиновой кислоты из уменьшенного в объеме раствора лизергиновой кислоты.14. Способ по п.13, где кристаллизацию ускоряют добавлением воды.15. Способ по п.13, дополнительно включающий выделение кристаллической А 2006133547 Ко РОССИЙСКАЯ ФЕДЕРАЦИЯ 19 11) мае см хх а (13 9 ВИ“ 2006 133 547 А (51) МПК С070 457/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2006133547/04, 17.02.2005 (71) Заявитель(и): ИВАКС ФАРМАСЬЮТИКАЛЗ с.р.о. (С2) (30) Конвенционный ...

Method of preparing d-2,6-dimethyl-8-cianmethylergoline or salts thereof

Process for the preparation of cabergoline

Method of producing derivatives of 8,8-disubstituted 6-methylergolines or their salts

Process for producing dihydrolisergol

Использование: е качестве промежуточного продукта в синтезе лекарств Сущность изобретени : продукт дигидролизергол, выход 93,9 - 98,5%, т.пл. 288&amp;deg;С (разл ). Реагент 1 лизергол Реагент 2 водород над палла- диевым катализатором на угле услови  реакции , в смеси N, N-диметилформамида и пиридина, при температуре от 40&amp;deg; до 80&amp;deg;С и давлении от 1 до 5 бар.

Microspheres having nucleus/coating structure

FIELD: medicine, pharmaceutics. SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents microspheres for treating schizophrenia, having a nucleus/coating structure and a spherical shape wherein the nucleus contains ariliprazol in the solid state, and the coating covers the entire surface or most of the nucleus and contains a biodegradable polymer. EFFECT: invention provides producing the microspheres of ariliprazol characterised by the high content and sustained release of the active substance, and preparing an injectable aqueous suspension of the above microspheres. 17 cl, 18 ex, 14 dwg

Process for preparing derivatives of 2-brom-alpha-ergo-cryptine

Method for performing anaesthesiological support of ophthalmological operations

FIELD: medicine. SUBSTANCE: invention relates to medicine, namely to anaesthesiology and ophthalmology. Anaesthesiological preparation of patients before operation is performed. Control of parameters of hemodynamics and estimation of obtained values of parameters are carried out. If before operation determined values of systolic arterial pressure are higher than 160 mmHg, nicergoline solution in dose 2 mg is introduced in intravenous bolus way. If values of systolic arterial pressure are higher than 180 mmHg, nicergoline is introduced in dose 4 mg. EFFECT: method makes it possible to provide stable hypotensive effect for several hours after operation without orthostatic effect, without causing sharp drop of arterial pressure at the time of preparation introduction, makes it possible to reduce postoperative oedema of cornea and increase vision acuity, as well as to increase threshold of pain sensitivity and stress resistance of patients. 2 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 612 099 C1 (51) МПК A61F 9/007 (2006.01) A61K 31/48 (2006.01) A61P 9/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2015156821, 29.12.2015 (24) Дата начала отсчета срока действия патента: 29.12.2015 Дата регистрации: (45) Опубликовано: 02.03.2017 Бюл. № 7 Адрес для переписки: 400138, г. Волгоград, ул. им. Землячки, 80, Волгоградский филиал ФГАУ "МНТК "Микрохирургия глаза" им. акад. С.Н. Федорова" Минздрава России (56) Список документов, цитированных в отчете о поиске: ДОЛИНА О.А. Анестезиология C 1 2 6 1 2 0 9 9 R U (54) Способ выполнения анестезиологического сопровождения офтальмологических операций (57) Формула изобретения Способ выполнения анестезиологического сопровождения офтальмологических операций, заключающийся в проведении анестезиологической подготовки пациентов перед операцией и контроле показателей гемодинамики перед операцией, оценке полученных значений показателей и введении ...

Method of producing n-alkylated dihydrolysergic acid

The present invention provides a process for preparing wherein R' is C 3 -C e alkyl, -CH 2 C 2 -C 4 alkenyl, propargyl, C 3 -C 8 cycloalkyl or C 1 -C 6 alkyl substituted C 3 -C 8 cycloalkyl; which comprises: reacting a compound of Formula (II): with a substituted benzenesulfonate of Formula III): wherein R' is as defined above and R 2 is hydrogen, bromo, methyl or nitro, in the presence of a base.

Process for preparing derivatives of ergol-8-ene or ergoline or their salts

The invention relates to new ergol-8-ene and ergoline derivatives of the general formula /I/ <IMAGE> /I/ wherein x y stands for -CH=C= or -CH2-CH= group, R stands for hydrogen atom or methyl group, R1 stands for hydrogen or halogen atom, R2 stands for lower alkylsulfonyloxy group, phenylsulfonyloxy group optionally substituted with a lower alkyl group, or azido group, R3 stands for lower alkylsulfonyloxy group or phenylsulfonyloxy group optionally substituted with a lower alkyl group, and acid addition salts thereof. These compounds can be prepared from compounds of the general formula II <IMAGE> /II/ wherein x y and R are as defined above, by reacting at least two equivalents of a lower alkylsulfonic acid chloride or phenylsulfonic acid chloride substituted with lower alkyl group. The resulting compound can be reacted with an alkali metal azide, and, if desired, the compound obtained is treated with a halogenating agent to form the 2-halogenide derivative, and, if desired, any resulting compound of general formula I is treated with an acid to form a therapeutically acceptable acid addition salt, or the free base is liberated from a salt. The compounds of general formula I possess valuable antiserotonine, antidepressant, dopamine receptor stimulant and hypotensive effects.

Method of extraction of alkaloids of ergot from cultural suspensions

Method of obtaining 8-thiomethyl-ergolines or salts thereof

Method of preparing lysergol derivatives

A novel process is disclosed for the preparation of derivatives of lysergol having the general formula: According to this process lysergol is directly used as the starting compound and, after the methylation at the 1 position of the corresponding 10 alpha-methoxy-lumilysergol, the methylated compound is directly esterified with a carboxylic acid R-COOH, the acid being selected in the group comprisig aliphatic, cycloatiphatic, aromatic, and heterocyclic carboxylic acids, containing up to 10 carbon atoms.

METHOD OF OBTAINING PEPTIDE-CONTAINING ERGOALKALOIDS

Method of producing 2-bromine derivatives of ergoalkaloids

Method for production of derivative of ergoline

FIELD: organic technology; pharmacology. SUBSTANCE: derivative of ergoline having formula I wherein R 1 -C 2 H 5 ,R 2 -(CH 2 ) 3 N(CH 3 ) 2 ,, R 3 is allyl, R 4 =R 5 =H is prepared by interaction of ergoline amide having formula II with 1-4 equivalents of isocyanate having formula III . In formulae II and III R 1 ,R 2 ,R 3 ,R 4 and R 5 are as mentioned above; interaction is carried out in 1,1-dichloroethane or in toluene at 35-60 C in the presence of CuCl and in the presence of phosphorous compound chosen of PPh 3 ,P(pClPh) 3 ,P(pMePh) 3 and MePh 2 P. Compounds having formula I are suitable as antiprolactinic and antiparcinsonic agents. EFFECT: improved efficiency of the method. ссср с ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2 118 323 Сл 51) М с 070 457/06, А 61 К 31/48 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 93058546/04, 15.02.1993 (30) Приоритет: 12.03.1992 СВ 9205439.4 (46) Дата публикации: 27.08.1998 (56) Ссылки: СВ, 2074566 А, С 070 457/06, 1981. СВ, 2103603 А, С ОГО 457/06, 1983. (71) Заявитель: Фармация энд Апджон, С.П.А. (Т) (72) Изобретатель: Илариа Кандиани (1Т), Уолтер Кабри (1Т), Анжело Бедески (!Т), Франко (54) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНОГО ЭРГОЛИНА (57) Реферат: Изобретение относится к улучшенному способу получения производного эрголита формулы |, где К. - С>Нё, К> - (СН). М (СН 3)2, Кз - аллил, Ка — К5 — Н, взаимодействием амида эрголита формулы 1 с 1 -4 эквивалентами изоцианата формулы Ш, где К, К К, № и КВ имеют вышеуказанные значения, в 1,1-дихлорэтане или толуоле, при {бот 35°С до 60°С в присутствии СичС! и соединения фосфора, выбранного из РРАз, Р(рОРП)5, Р(рМеРп)з и МеРп->Р. Соединения | являются полезными в качестве антипролактиновых и антипаркинсоновых агентов. м Зарини (1Т) (73) Патентообладатель: < Фармация энд Апджон С.П.А. (1Т) о © сч © со == ТТ, == Сс' > 0 ТТТ Способ выполняется при более мягких условиях, с меньшим избытком изоционата, а продукт | получают с более высокой ...

Method of producing tert-butyl-derivative of ergoline

Ergoline derivatives of general formula I <CHEM> wherein either R1 represents a hydrogen atom or a methoxy group and R2 represents a hydrogen atom or R1 and R2 taken together represent a chemical bond, and R3 represents a hydrogen atom, an unsubstituted or substituted nicotinoyl group or a 1-oxo-2-cyclopenten-3-yl group; or a pharmaceutically acceptable salt thereof are active at the Central Nervous System level and useful therefore in the treatment of cerebral insufficiency and senile dementia.

Process for preparing ergolin derivatives

Ergoline derivatives of formula (I) …<CHEM>… wherein R1 represents a hydrogen atom or a methyl group, R2 represents a hydrogen atom or a methoxy group, X represents an oxygen or sulphur atom or a NH or NCH3 group, R3 represents a hydrogen atom, a trifluoromethyl or phenyl group or an alkyl group having from 1 to 4 carbon atoms, R4 represents a hydrogen atom, a methyl or acetyl group or an alkyl group having from 1 to 4 carbon atoms, or R3 and R4 together represent a 3 or 4 membered carbon atom chain, Y represents an electron withdrawing group such as a cyano, nitro, alkylsulphonyl or alkylsulphinyl group or a group of the formula COR5 wherein R5 represents an alkyl group having from 1 to 4 carbon atoms or a phenyl, alkoxy, amino or N-substituted amino group or R5 an R3 together represent a 2 or 3 membered carbon atom chain, R6 represents a hydrocarbon group having from 1 to 4 carbon atoms or a benzyl or phenethyl group, and R7 represents a hydrogen or halogen atom or a methyl or formyl group or a group of the formula SR8 wherein R8 represents an alkyl group having from 1 to 4 carbon atoms or a phenyl group. The pharmaceutically acceptable addition salts and their preparation are disclosed. In form of therapeutical compositions the compounds exhibit useful pharmacological properties.

Improved preparation method of nicergoline

本发明涉及一种尼麦角林的改进制备方法，该方法包括以下步骤：(1)在适量浓硫酸催化和紫外光照射条件下，使麦角醇与甲醇进行光反应，制得10α‑甲氧基光麦角醇；(2)在酰胺类非质子溶剂中，加入无机碱，使10α‑甲氧基光麦角醇与碘甲烷进行甲基化反应生成1‑甲基‑10α‑甲氧基光麦角醇；(3)在溶剂中，以有机胺为缚酸剂，将5‑溴烟酸与草酰氯反应制得5‑溴烟酰氯中间体，再将5‑溴烟酰氯中间体与1‑甲基‑10α‑甲氧基光麦角醇进行缩合反应，制得尼麦角林。与现有技术相比，本发明反应无需惰性气体保护、酸用量小、反应副产物易回收利用，产品最终产率能达到50％以上，产品纯度99％以上，适合规模化生产。

Method of preparing ergoline derivatives

New ergoline derivatives are disclosed which are compounds of formula (I) having the structure: <IMAGE> (I) wherein R1 is hydrogen or methoxy; R2 is hydrogen or methyl; and X is hydroxy, R3COO, S-R4 or NR5R6 in which R3 is a straight or branched alkyl having from 1 to 6 carbon atoms, unsubstituted- or substituted-phenyl, the substituents being selected from the class consisting of chlorine, bromine, alkyl or alkoxy having from 1 to 4 carbon atoms, cycloalkyl containing from 3 to 6 carbon atoms, or a heterocycle; R4 is phenyl or a heterocycle, and R5 and R6 are alkyl having from 1 to 4 carbon atoms, or together with the N atom to which they are attached, forming a heterocycle. The heterocycle may be a 5- or 6-membered ring which contains from 1 to 3 hetero atoms selected from the class consisting of nitrogen, oxygen and sulphur, and may be saturated or unsaturated, and unsubstituted or substituted by halogen, alkyl having from 1 to 3 carbon atoms, hydroxy, nitro, amino, CONHNH2 and COOH.

Process for preparing derivatives of ergoi-8-ene or ergoline or their salts

The invention relates to new ergol-8-ene and ergoline derivatives of the general formula /I/ <IMAGE> /I/ wherein x y stands for -CH=C= or -CH2-CH= group, R stands for hydrogen atom or methyl group, R1 stands for hydrogen or halogen atom, R2 stands for lower alkylsulfonyloxy group, phenylsulfonyloxy group optionally substituted with a lower alkyl group, or azido group, R3 stands for lower alkylsulfonyloxy group or phenylsulfonyloxy group optionally substituted with a lower alkyl group, and acid addition salts thereof. These compounds can be prepared from compounds of the general formula II <IMAGE> /II/ wherein x y and R are as defined above, by reacting at least two equivalents of a lower alkylsulfonic acid chloride or phenylsulfonic acid chloride substituted with lower alkyl group. The resulting compound can be reacted with an alkali metal azide, and, if desired, the compound obtained is treated with a halogenating agent to form the 2-halogenide derivative, and, if desired, any resulting compound of general formula I is treated with an acid to form a therapeutically acceptable acid addition salt, or the free base is liberated from a salt. The compounds of general formula I possess valuable antiserotonine, antidepressant, dopamine receptor stimulant and hypotensive effects.

Novel iso-ergoline derivatives

Provided herein are novel iso-ergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT

Novel neuromodulatory compounds

Provided herein are novel neuromodulatory compounds and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine and Parkinson's disease, using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT

Novel preparation method of nicergoline

本发明涉及一种尼麦角林的新制备方法，该方法包括以下步骤：(1)在极性非质子溶剂中，加入无机碱，使麦角醇(II)与甲基化试剂进行甲基化反应，生成1‑甲基麦角醇(III)；(2)1‑甲基麦角醇(III)与甲醇在浓硫酸的催化下进行光反应，制得1‑甲基‑10α‑甲氧基光麦角醇(IV)；(3)在极性非质子有机溶剂中，以N,N’‑羰基二咪唑为缩合剂，将5‑溴烟酸(V)与N,N’‑羰基二咪唑先反应制得5‑溴烟酰咪唑(VI)中间体，再将5‑溴烟酰咪唑(VI)中间体与1‑甲基‑10α‑甲氧基光麦角醇(IV)进行缩合反应，制得尼麦角林(I)。与现有技术相比，本发明无需惰性气体保护、酸用量小、产品质量好、收率高、反应副产物易回收利用，适合工业化生产。

Pharmaceutical dosage forms comprising a low-solubility drug and a polymer

A dosage form comprises a low-solubility drug, and a precipitation-inhibiting polymer. The drug is in a solubility-improved form and in the form of particles at least partially coated with the precipitation-inhibiting polymer. Exemplified low-solubility drugs are ziprasidone and sildenafil. Exemplified precipitation-inhibiting polymer is HPMCAS.

Process for producing derivatives of 6-methyl-8-beta-hydrazinomethylergolin or their salts

The invention relates to new 8 beta -hydrazinomethyl-ergoline derivatives of the general formula (I), <IMAGE> (I) wherein x y stands for a <IMAGE> or <IMAGE> group, R stands for hydrogen or methyl group, and R1 stands for hydrogen, a lower acyl group, a di-(lower-alkylaminocarbonyl group, a group of the general formula (VI), <IMAGE> (VI) wherein Z1, Z2 and Z3 each represent hydrogen, halogen or a trifluoromethyl group, or a group of the general formula (VII), <IMAGE> (VII) wherein Y represents a lower alkyl group, allyl group or phenyl group, and acid addition salts thereof. These compounds possess valuable antiserotonine, antidepressant and hypotensive effects, furthermore they can be applied as starting substances in the preparation of other biologically active ergoline derivatives. The new compounds of the general formula (I) are prepared according to the invention by reacting the respective 6-methyl-8 beta -mesyloxymethyl or -tosyloxymethyl-ergoline derivatives with dry hydrazine. In order to obtain the N-substituted hydrazinomethyl compounds, the N-unsubstituted derivatives are reacted with an acylating agent or with an isothiocyanate.

Method of obtaining 2-brom-alpha-ergocryptine or acid-additive salts thereof

The invention relates to a novel process for the halogenation in 2-position of ergot alkaloids. The process is characterized by that as a halogenating agent a system consisting of dimethylsulfoxide, a trialkylhalosilane or triarylhalosilane and optionally a hydrogen halide is used.

Method of obtaining derivatives of 8-(bis-aminoethyl)-ergoline-1 and their salts

Process for the preparation of ergoline derivatives

본 발명은 일반식(Ⅱ)의 에르골린 아미드를 금속촉매 및 인 화합물의 존재하에 일반식(Ⅲ)의 이소시아네이트와 반응시킴을 포함하여, 일반식(I)의 에르골린 유도체를 제조하는 방법에 관한 것이다. The present invention relates to a method for preparing an ergoline derivative of formula (I), comprising reacting an ergoline amide of formula (II) with an isocyanate of formula (III) in the presence of a metal catalyst and a phosphorus compound will be. 일반식(I)의 화합물은 유용한 항프롤락틴제 및 파킨슨병 치료제이다. Compounds of formula (I) are useful antiprolactin agents and therapeutic agents for Parkinson's disease.

1-Alkyl-ergolinyl-thiourea derivative, process for producing the same and drug having central α-lower 2 receptor-blocking action containing the same

Aripiprazol pharmaceutical solution for oral using

FIELD: medicine, pharmacy, medicinal agents. SUBSTANCE: invention relates to aripiprazol pharmaceutical solutions used in oral using and designated for treatment of schizophrenia. Proposed agent comprises aripiprazol, pharmaceutically useful system of solvents, one or more taste-improving/masking agents and one or more acids chosen from group consisting of lactic, acetic, tartaric and citric acid and wherein pH of proposed pharmaceutical solution is from 2.5 to 4.5. Invention provides dissolving difficultly soluble medicinal agent and to compensate aripiprazol bitter taste and to obtain stable solution of this substance. EFFECT: improved properties of agent. 17 cl, 2 tbl, 3 ex ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß RU (19) (11) 2 295 960 (13) C2 (51) ÌÏÊ A61K 31/496 (2006.01) A61K 9/08 (2006.01) A61P 25/18 (2006.01) ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÎÏÈÑÀÍÈÅ ÈÇÎÁÐÅÒÅÍÈß Ê ÏÀÒÅÍÒÓ (21), (22) Çà âêà: 2003132426/15, 24.04.2002 (72) Àâòîð(û): ÏÀÐÀÁ Ïðàêàø (US), ×ÎÓ Äæîéñ (US) (24) Äàòà íà÷àëà îòñ÷åòà ñðîêà äåéñòâè ïàòåíòà: 24.04.2002 (73) Ïàòåíòîîáëàäàòåëü(è): ÁÐÈÑÒÎË-ÌÀÅÐÑ ÑÊÂÈÁÁ ÊÎÌÏÀÍÈ (US) R U (30) Êîíâåíöèîííûé ïðèîðèòåò: 25.04.2001 (ïï.1-17) US 60/286,718 (43) Äàòà ïóáëèêàöèè çà âêè: 20.04.2005 (45) Îïóáëèêîâàíî: 27.03.2007 Áþë. ¹ 9 2 2 9 5 9 6 0 2 2 9 5 9 6 0 R U (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 31.10.2003 C 2 C 2 (56) Ñïèñîê äîêóìåíòîâ, öèòèðîâàííûõ â îò÷åòå î ïîèñêå: US 5006528 À, 09.04.1991. RU 2097039 Ñ1, 27.11.1997. OSHIRO Y., SATO S., KURAHASHI N. et al. Novel antipsychotic agents with dopamine autoreceptor agonist properties: synthesis and pharmacology of 7-[4-(4-phenyl1-piperazmyl)butoxy]-3,4-dihydro-2(1H)quinolinone derivatives. - J Med Chem. 1998 Feb 26;41(5):658-67. - [Àâòîðåôåðàò ÀÁÄ Medline]. (86) Çà âêà PCT: US 02/13048 (24.04.2002) (87) Ïóáëèêàöè PCT: WO 02/085366 (31.10.2002) Àäðåñ äë ïåðåïèñêè: 119034, Ìîñêâà, Ïðå÷èñòåíñêèé ïåð., 14, ñòð.1, 4 ýòàæ, "Ãîóëèíãç Èíòåðíýøíë Èíê.", Þ.Â.Äåìåíòüåâîé ( ...

Method of preparing lysergic acid amides or salts thereof

Process for preparing ergoline derivatives or their salts

A description is given of the preparation of ergolene derivatives with an action lowering blood pressure and the formula I <IMAGE> in which R1 and R2 are each hydrogen or an alkyl group with 1 to 4 carbon atoms, or else together form an alkylidene chain with a maximum of 5 carbon atoms, and their salts with acids. Corresponding compounds unsaturated in position 2,3 are reduced selectively in position 2,3 and the resulting compounds of the formula I are converted where appropriate into their acid addition salts.

Method of obtaining 6-methyl-8beta-(substituted)-methylergolines or their salts

Method of producing ergoline derivative

Изобретение касаетс  производных эрголина, в частности получени  10-метокси-1,6-диметил-8β-(1-C 1 -C 4 -алкил-1,4-дигидро-3-пиридилкарбонилоксиметил)-эрголинов, которые обладают активностью в отношении центральной нервной системы и могут быть использованы дл  лечени  метаболических сосудистых церебральных нарушений. Цель - создание новых активных веществ указанного класса. Их синтез ведут восстановлением четвертичной галоидной соли эрголина с помощью дитионита натри  в слабоосновном водном растворе при 5-25°С. Новые соединени  малотоксичны (LD 50 *98800 мг/кг) и могут быть использованы по указанному назначению. 1 табл.

Mental illness therapeutic agent having il-6 inhibitor as active ingredient

Method of obtaining n-b-substituted derivatives of 8-(b-aminoethyl) ergolin-1 or their salts

8,8-Disubstituted-6-methylergolines and related compounds

8,8-Disubstituted-6-methylergolines and 9-ergolenes, prepared by alkylation of lysergic, isolysergic or their 9,10-dihydro analogues, optionally followed by chemical modification of an 8-substituent.

TREATMENT OF SCHIZOPHRENIA AND PSYCHOSIS

ERGOLINE DERIVATIVES, PROCESS FOR PREPARING THEM AND THEIR USE AS MEDICAMENTS

DERIVES DE L'ERGOLINE, PROCEDE POUR LES PREPARER ET LEUR EMPLOI COMME MEDICAMENTS. CES COMPOSES REPONDENT A LA FORMULE I: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE METHYLE, R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE METHOXY, X REPRESENTE UN ATOME D'OXYGENE OU DE SOUFRE OU UN GROUPE NH OU NCH, R REPRESENTE UN ATOME D'HYDROGENE, UN GROUPE TRIFLUOROMETHYLE OU PHENYLE OU UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE, R REPRESENTE UN ATOME D'HYDROGENE, UN GROUPE METHYLE OU ACETYLE, UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE, OU R ET R REPRESENTENT ENSEMBLE UNE CHAINE PRESENTANT 3 OU 4 ATOMES DE CARBONE, Y REPRESENTE UN GROUPE DE RETRAIT D'ELECTRON TEL QU'UN GROUPE CYANO, NITRO, ALKYSULFONYLE OU ALKYLSULFINYLE OU UN GROUPE DE FORMULE COR DANS LAQUELLE R REPRESENTE UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE OU UN GROUPEPHENYLE, ALCOXY, AMINO OU AMINO N-SUBSTITUE, OU R ET R REPRESENTENT ENSEMBLE UNE CHAINE PRESENTANT 2 OU 3 ATOMES DE CARBONE, R REPRESENTE UN GROUPE D'HYDROCARBURE AYANT DE 1 A 4 ATOMES DE CARBONE OU UN GROUPE BENZYLE OU PHENETHYLE, R REPRESENTE UN ATOME D'HYDROGENE OU D'HALOGENE OU UN GROUPE METHYLE OU FORMYLE OU UN GROUPE DE FORMULE SR DANS LAQUELLE R REPRESENTE UN GROUPE ALKYLE AYANT DE 1 A 4 ATOMES DE CARBONE OU UN GROUPE PHENYLE. LEUR PREPARATION SE FAIT PAR CONDENSATION DANS L'HEXAMETHYLPHOSPHOTRIAMIDE D'UN INTERMEDIAIRE APPROPRIE DE FORMULE II: (CF DESSIN DANS BOPI) DANS LAQUELLE R, R, R ET R ONT LA SIGNIFICATION DONNEE DANS LA REVENDICATION 1, AVEC UN SEL ALCALIN D'UN COMPOSE DE FORMULE III: (CF DESSIN DANS BOPI) DANS LAQUELLE R, R, X ET Y ONT LA SIGNIFICATION INDIQUEE DANS LA REVENDICATION 1, APRES QUOI, SI ON LE DESIRE, ON AJOUTE UN ACIDE ORGANIQUE OU INORGANIQUE POUR OBTENIR UN SEL D'ADDITION. ERGOLINE DERIVATIVES, PROCESS FOR PREPARING THEM AND THEIR USE AS MEDICINAL PRODUCTS. THESE COMPOUNDS MEET FORMULA I: (CF DRAWING IN ...

Patent FR2297628B1

Patent FR2453642B1

PROCESS FOR THE PREPARATION OF N-METHYL DERIVATIVES OF METHYL DIHYDROLYSERGATE OR METHYL METHOXYLUMILYSERGATE

Patent FR2293204B1

N- (8A-ERGOLINYL) -N ', N'-DIETHYLUREES, 1-SUBSTITUTED AND PROCESS FOR OBTAINING THESE COMPOUNDS

A.L'INVENTION CONCERNE DES PRODUITS CHIMIQUES NOUVEAUX PRESENTANT UNE ACTIVITE PHARMACEUTIQUE. B.CES PRODUITS SONT CONSTITUES PAR LES N-(8A-ERGOLINYL)-N,N-DIETHYLUREES SUBSTITUEES EN 1, DE FORMULE GENERALE I: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE UN GROUPE ALCOYLE AVEC 1 A 4 ATOMES DE CARBONE ET R REPRESENTE UN GROUPE ALCOYLE INFERIEUR AVEC 1 A 4 ATOMES DE CARBONE, UN GROUPE BENZYLE, UN GROUPE ALLYLE OU UN GROUPE DE FORMULE GENERALE-(CH)COOR, OU R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE ALCOYLE AVEC 1 A 2 ATOMES DE CARBONE, ET N EST UN NOMBRE ENTIER DE 1 A 4. C.CES PRODUITS PRESENTENT DES PROPRIETES INTERESSANTES COMME INHIBITEURS DE LA SECRETION DE PROLACTINE ET DE L'HORMONE DE CROISSANCE ET COMME STIMULATEURS DE LA SECRETION DE GONADOTROPINES CHEZ L'ANIMAL. A. THE INVENTION RELATES TO NEW CHEMICALS SHOWING PHARMACEUTICAL ACTIVITY. B. THESE PRODUCTS CONSTITUTE THE N- (8A-ERGOLINYL) -N, N-DIETHYLUREES SUBSTITUTED IN 1, OF GENERAL FORMULA I: (CF DRAWING IN BOPI) IN WHICH R REPRESENTS AN ALCOHYL GROUP WITH 1 TO 4 CARBON ATOMS AND R REPRESENTS A LOWER ALCOYL GROUP WITH 1 TO 4 CARBON ATOMS, A BENZYL GROUP, AN ALLYL GROUP OR A GROUP OF GENERAL FORMULA- (CH) COOR, OR R REPRESENTS A HYDROGEN ATOM OR AN ALCOYL GROUP WITH 1 TO 2 CARBON ATOMS, AND N IS A WHOLE NUMBER FROM 1 TO 4. C. THESE PRODUCTS SHOW INTERESTING PROPERTIES AS INHIBITORS OF PROLACTIN AND GROWTH HORMONE SECRETION AND AS STIMULATORS OF GONADOTROPIN SECRETION IN ANIMALS.

New derivatives of 6-methyl- and 1,6-dimethyl-ergoline i.

Process for the preparation of n- / d-6-methyl-8-isoergolényl / -n ', n'-diethyl-urea

New derivatives of the lysergic acid series and their preparation

PROCESS FOR BROMINATING ALKALOIDS IN RYE ERGOT AND COMPOUNDS OBTAINED

L'INVENTION CONCERNE UN PROCEDE DE PREPARATION DES ALCALOIDES DE L'ERGOT DE SEIGLE DE FORMULE: (CF DESSIN DANS BOPI) DANS LAQUELLE R REPRESENTE UN GROUPE CARBOXY, ALCOXY-CARBONYLE, CARBAMOYLE EVENTUELLEMENT SUBSTITUE, OU UN GROUPE CARBAMOYLE SUBSTITUE PAR UN RESTE PEPTIDIQUE APPARTENANT AUX ALCALOIDES DE L'ERGOT DE SEIGLE. SELON LE PROCEDE DE L'INVENTION, ON BROME UN COMPOSE CORRESPONDANT DE FORMULE: (CF DESSIN DANS BOPI) PAR REACTION AVEC UN COMPLEXE DE BROME DE LA 3-BROMO-6-CHLORO-2-METHYL-IMIDAZO1,2-BPYRIDAZINE. CE PROCEDE PERMET DE BROMER SELECTIVEMENT LES ALCALOIDES DE L'ERGOT DE SEIGLE. THE INVENTION CONCERNS A PROCESS FOR THE PREPARATION OF ALKALOIDS FROM RYE ERGOT OF FORMULA: (CF DRAWING IN BOPI) IN WHICH R REPRESENTS A CARBOXY, ALCOXY-CARBONYL, CARBAMOYL, POSSIBLY SUBSTITUTED, OR A SMALL CARBAMOYL GROUP. BELONGING TO THE ALKALOIDS OF ERGOT OF RYE. ACCORDING TO THE PROCESS OF THE INVENTION, A CORRESPONDING COMPOUND OF FORMULA: (CF DRAWING IN BOPI) IS BROMINATED BY REACTION WITH A 3-BROMO-6-CHLORO-2-METHYL-IMIDAZO1,2-BPYRIDAZINE BROMINE COMPLEX. THIS PROCESS ALLOWS SELECTIVELY BROMING THE ALKALOIDS OF RYE ERGOT.

2,3-DIHYDROERGOLINS