Details for Patent: 8,921,393
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Title: | Selective serotonin 2A/2C receptor inverse agonists as therapeutics for neurodegenerative diseases |
Abstract: | Behavioral pharmacological data with the compound of formula (I), a novel and selective 5HT2A/2C receptor inverse agonist, demonstrate in vivo efficacy in models of psychosis and dyskinesias. This includes activity in reversing MK-801 induced locomotor behaviors, suggesting that this compound may be an efficacious anti-psychotic, and activity in an MPTP primate model of dyskinesias, suggesting efficacy as an anti-dyskinesia agent. These data support the hypothesis that 5HT2A/2C receptor inverse agonism may confer antipsychotic and anti-dyskinetic efficacy in humans, and indicate a use of the compound of formula (I) and related agents as novel therapeutics for Parkinson's Disease, related human neurodegenerative diseases, and psychosis. |
Inventor(s): | Weiner; David M. (San Diego, CA), Davis; Robert E. (San Diego, CA), Brann; Mark R. (Rye, NH), Andersson; Carl-Magnus A. (Hjarup, SE), Uldam; Allan K. (Vaerloese, DK) |
Assignee: | ACADIA Pharmaceuticals Inc. (San Diego, CA) |
Filing Date: | Nov 21, 2013 |
Application Number: | 14/086,838 |
Claims: | 1. A method for treating a neurodegenerative disease, or a symptom thereof, comprising administering to a patient suffering from a neurodegenerative disease, or a symptom thereof, a therapeutically effective amount of a compound of formula (I): ##STR00010## or a pharmaceutically acceptable salt thereof. 2. The method of claim 1, wherein the salt is a tartrate salt. 3. The method of claim 1, wherein the salt is a hydrochloride salt. 4. The method of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is from about 0.001 mg to about 50 mg. 5. The method of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is from about 1 mg to about 10 mg. 6. The method of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is about 10 mg. 7. The method of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is about 25 mg. 8. The method of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is about 50 mg. 9. The method of claim 1, wherein the compound of formula (I) is administered daily. 10. The method of claim 1, wherein the compound of formula (I) is administered once daily. 11. The method of claim 1, wherein the neurodegenerative disease is selected from the group consisting of Parkinson's disease, Huntington's disease, Alzheimer's disease, Spinocerebellar Atrophy, Tourette's Syndrome, Friedrich's Ataxia, Machado-Joseph's disease, Lewy Body Dementia, Dystonia, Progressive Supranuclear Palsy, and Frontotemporal Dementia. 12. The method of claim 1, wherein the neurodegenerative disease is Parkinson's disease. 13. The method of claim 1, wherein the neurodegenerative disease is Alzheimer's disease. 14. The method of claim 12, wherein a tartrate salt of the compound of formula (I) is administered. 15. The method of claim 13, wherein a tartrate salt of the compound of formula (I) is administered. 16. The method of claim 1, wherein the symptom is psychosis secondary to the neurodegenerative disease. 17. The method of claim 14, wherein the symptom is psychosis secondary to the neurodegenerative disease. 18. The method of claim 15, wherein the symptom is psychosis secondary to the neurodegenerative disease. 19. A method for treating psychosis secondary to a neurodegenerative disorder, comprising administering to a patient suffering from a neurodegenerative disorder, a therapeutically effective amount of a compound of formula (I): ##STR00011## or a pharmaceutically acceptable salt thereof. 20. The method of claim 19, wherein the salt is a tartrate salt. 21. The method of claim 19, wherein the salt is a hydrochloride salt. 22. The method of claim 19, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is from about 0.001 mg to about 50 mg. 23. The method of claim 19, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is from about 1 mg to about 10 mg. 24. The method of claim 19, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is about 10 mg. 25. The method of claim 19, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is about 25 mg. 26. The method of claim 19, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is about 50 mg. 27. The method of claim 19, wherein the compound of formula (I) is administered daily. 28. The method of claim 19, wherein the compound of formula (I) is administered once daily. 29. The method of claim 19, wherein the compound of formula (I) is administered in combination with an additional therapeutic agent. 30. The method of claim 29, wherein the additional therapeutic agent is selected from the group consisting of levodopa, bromocriptine, pergolide, ephedrine sulfate, pemoline, mazindol, d,1-.alpha.-methylphenethylamine, methylphenidate, pramipexole, modafinil, and ropinirole. 31. The method of claim 29, wherein the additional therapeutic agent is an anti-dyskinesia agent. 32. The method of claim 29, wherein the additional therapeutic agent is an anti-dyskinesia agent selected from the group consisting of baclofen, botulinum toxin, clonazepam, and diazepam. 33. The method of claim 29, wherein the additional therapeutic agent is an anti-dystonia, anti-myoclonus, or anti-tremor agent selected from the group consisting of baclofen, botulinum toxin, clonazepam, and diazepam. 34. The method of claim 29, wherein the additional therapeutic agent is an anti-psychotic agent with dopaminergic receptor antagonism. 35. The method of claim 29, wherein the additional therapeutic agent is an anti-psychotic agent selected from the group consisting of chlorpromazine, haloperidol, molindone, thiordazine, a phenothiazine, a butyrophenone, diphenylbutylpiperidine, thioxanthines, substituted benzamides, sertindole, amisulpride, ziprasidone, aripiprazole, clozapine, olanzapine, risperidone, N-desmethylclozapine, N-desmethylolanzapine, and 9-OH-risperidone. 36. The method of claim 29, wherein the diphenylbutylpiperidine is pimozide, the thioxanthine is fluphenthixol, and the substituted benzamide is sulpiride. |