IN-VIVO OCCUPATION OF DOPAMINE D-1, D-2 AND SEROTONIN (5-HT)(2A) RECEPTORS BY SERTINDOLE IN THE RAT-BRAIN

Objective: To determine the in vivo occupation of dopamine D-1, D-2 an d serotonin (5-MT)(2A) receptors by novel antipsychotic agent sertindo le using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irr eversible antagonist at these receptor sites. Design: Animal study. in terventions: Intraperitoneal administration to Wistar rats of I of 4 t est compounds: a control compound of 0.15% tartaric acid, or a compoun d of either sertindole (0.5 mg/kg or 2.0 mg/kg) or clozapine (20 mg/kg ) dissolved in 0.15% tartaric acid I hour before intraperitoneal admin istration of EEDQ (0 mg/kg) or ethanol/water solution. Results: Sertin dole exhibited little or no effect on D and D, binding sites in vivo. On the other hand, sertindole occupied 5-HT2A receptors more extensive ly and firmly than EEDQ. This study indicates that sertindole is chara cterized by high occupancy of 5-HT2A receptors and by low or minimum o ccupancy of D-1 and D-2 receptors. Conclusions: These characteristics are very similar to atypical antipsychotic agents such as clozapine. S ertindole's low liability to cause extrapyramidal side effects (EPS) m ay be related to greater long-term binding for 5-HT2A receptors relati ve to D-2 receptors.