Binding of Antipsychotic Drugs to Cortical 5-HT_2A Receptors: A PET Study of Chlorpromazine, Clozapine, and Amisulpride in Schizophrenic Patients

OBJECTIVE: This study examined the binding to cortical serotonin 5-HT_2A receptors of conventional doses of the typical neuroleptic chlorpromazine in comparison with clozapine, the prototype atypical antipsychotic, and amisulpride, a specific dopamine D₂-D₃ blocker. METHOD: Seventeen schizophrenic patients treated with chlorpromazine (75–700 mg/day), four treated with clozapine (200–600 mg/day), and five treated with amisulpride (200–1200 mg/day) were studied. Cortical 5-HT_2A binding was estimated by reference to the values for 14 antipsychotic-free schizophrenic subjects with the use of positron emission tomography and [¹⁸F]setoperone, a high-affinity radioligand for cortical 5-HT_2A receptors. RESULTS: A dose-dependent decrease in the number of available cortical binding sites for [¹⁸F]setoperone was demonstrated in the chlorpromazine group; for the highest dose, there was a virtual lack of sites 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-HT_2A blockade with both clozapine and high doses of chlorpromazine. No significant binding of amisulpride to 5-HT_2A receptors was detected. CONCLUSIONS: A high level of 5-HT_2A receptor blockade does not appear specific to clozapine in comparison with high doses of chlorpromazine, suggesting that the distinct clinical profiles of both drugs are unrelated to 5-HT_2A blockade itself.