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 agonist may confer antipsychotic and ant 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.

1 - 86 . (canceled) 
     
     
         87 . A method of treating Parkinson's Disease psychosis in a patient in need thereof, comprising orally administrating to the patient a pharmaceutical composition comprising from about 10 mg to about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof once daily. 
     
     
         88 . The method of  claim 87 , wherein the salt is a tartrate salt. 
     
     
         89 . A method of treating psychosis secondary to a neurodegenerative disorder in a patient in need thereof, comprising orally administrating to the patient a pharmaceutical composition comprising from about 10 mg to about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof once daily. 
     
     
         90 . The method of  claim 89 , wherein the salt is a tartrate salt. 
     
     
         91 . The method of  claim 89 , wherein the neurodegenerative disorder is Alzheimer's Disease. 
     
     
         92 . The method of  claim 89 , wherein the neurodegenerative disorder is dementia. 
     
     
         93 . The method of  claim 89 , wherein the neurodegenerative disorder is Parkinson's Disease. 
     
     
         94 . A method of treating a neurodegenerative disease in a patient in need thereof, comprising orally administrating to the patient a pharmaceutical composition comprising from about 10 mg to about 50 mg of N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide or a pharmaceutically acceptable salt thereof once daily, 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. 
     
     
         95 . The method of  claim 94 , wherein the salt is a tartrate salt. 
     
     
         96 . The method of  claim 94 , wherein the neurodegenerative disease is Parkinson's disease. 
     
     
         97 . The method of  claim 94 , wherein the neurodegenerative disease is Alzheimer's disease.