BINDING OF ANTIPSYCHOTIC-DRUGS TO CORTICAL 5-HT2A RECEPTORS - A PET STUDY OF CHLORPROMAZINE, CLOZAPINE, AND AMISULPRIDE IN SCHIZOPHRENIC-PATIENTS

Objective: This study examined the binding to cortical serotonin 5-HT2 A receptors of conventional doses of the typical neuroleptic chlorprom azine in comparison with clozapine, the prototype atypical antipsychot ic, and amisulpride, a specific dopamine D-2-D-3 blocker. Method: Seve nteen schizophrenic patients treated with chlorpromazine (75-700 mg/da y), four treated with clozapine (200-600 mg/day), and five treated wit h amisulpride (200-1200 mg/day) were studied. Cortical 5-HT2A binding was estimated by reference to the values for 14 antipsychotic-free sch izophrenic subjects with the use of positron emission tomography and [ F-18]setoperone, a high-affinity radioligand for cortical 5-HT2A recep tors. Results: A dose-dependent decrease in the number of available co rtical binding sites for [F-18]setoperone was demonstrated in the chlo rpromazine group; for the highest dose, there was a virtual lack of si tes available for binding. A very low percentage of available binding sites was also observed in the clozapine-treated patients at all doses . This suggests a high level of 5-HT2A blockade with both clozapine an d high doses of chlorpromazine. No significant binding of amisulpride to 5-HT2A receptors was detected. Conclusions: A high level 5-HT2A rec eptor blockade does not appear specific to clozapine in comparision wi th high doses of chlorpromazine, suggesting that the distinct clinical profiles of both drugs are unrelated to 5-HT2A blockade itself.