title: Effect of amperozide on rat cortical 5-HT2 and striatal and limbic dopamine D2 receptor occupancy: implications for antipsychotic action.
abstract: Amperozide (FG 5606, N-ethyl-4-[4',4'-bis(p-fluorophenyl)butyl]-1-piperazine-carboxamide) is an atypical antipsychotic drug which has relatively weak in vitro affinity for striatal dopamine2 (D2) receptors and strong affinity for cortical 5-HT2 receptors. The in vivo affinity for 5-HT2 binding sites in rat cortex was 1.1 mg/kg. In striatum or olfactory tubercle, doses of amperozide up to 40 mg/kg did not displace radioligand binding to D2 receptors. Amperozide, haloperidol and ritanserin had similar in vivo potency in blocking the 5-HT2 binding site, but only haloperidol displaced D2 receptor binding. Based on the clinically effective dose of amperozide (0.14-0.28 mg/kg per day), it is suggested that the antipsychotic effect of amperozide is related, in part, to its in vivo interaction with the 5-HT2 receptor and that amperozide cannot be expected to exert its antipsychotic action by blockade of D2 receptors in the striatum or limbic regions.
authors.affiliation: Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH.
authors.forename: H Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: C A
authors.initials: CA
authors.lastname: Stockmeier
mesh_terms: D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology
chemical_list: D010879:Piperazines; D011619:Psychotropic Drugs; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; C049058:amperozide; D016713:Ritanserin; D006220:Haloperidol