Effect of amperozide on rat cortical 5-HT₂ and striatal and limbic dopamine D₂ receptor occupancy: Implications for antipsychotic action

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.