Details for Patent: 7,732,462

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:	May 03, 2006
Application Number:	11/416,527
Claims:	1. A method of treating schizophrenia in a patient, comprising administering to a patient having schizophrenia a therapeutically effective amount of (a) N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof, and (b) risperidone. 2. A method of treating schizophrenia in a patient, comprising administering to the patient having schizophrenia a therapeutically effective amount of (a) N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof, and (b) haloperidol. 3. A method for reducing an amount of haloperidol or risperidone effective to treat psychosis in a schizophrenic patient, the method comprising administering a therapeutically effective amount of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, to the schizophrenic patient with psychosis being treated with haloperidol or risperidone. 4. The method of claim 1, wherein the tartrate salt of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide is administered. 5. The method of claim 2, wherein the tartrate salt of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide is administered. 6. The method of claim 3, wherein the tartrate salt of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide is administered. 7. The method of claim 1, wherein about 0.01 mg/kg of body weight to about 2 mg/kg body weight of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof is administered. 8. The method of claim 2, wherein about 0.01 mg/kg of body weight to about 2 mg/kg body weight of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof is administered. 9. The method of claim 3, wherein about 0.01 mg/kg of body weight to about 2 mg/kg body weight of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof is administered. 10. The method of claim 1, wherein about 10 mg to about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 11. The method of claim 2, wherein about 10 mg to about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 12. The method of claim 3, wherein about 10 mg to about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 13. The method of claim 10, wherein about 10 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 14. The method of claim 10, wherein about 25 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 15. The method of claim 10, wherein about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 16. The method of claim 11, wherein about 10 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 17. The method of claim 11, wherein about 25 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 18. The method of claim 11, wherein about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 19. The method of claim 12, wherein about 10 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 20. The method of claim 12, wherein about 25 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 21. The method of claim 12, wherein about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide, or a pharmaceutically acceptable salt thereof, is administered. 22. The method of claim 1, wherein the hydrochloride salt of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide is administered. 23. The method of claim 2, wherein the hydrochloride salt of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide is administered. 24. The method of claim 3, wherein the hydrochloride salt of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyl- oxy)phenylmethyl)carbamide is administered.