PET analysis indicates atypical central dopamine receptor occupancy in clozapine-treated patients.
D1 and D2 dopamine (DA) receptor occupancy was determined by PET in the basal ganglia of drug-treated schizophrenic patients. In 22 patients treated with classical neuroleptics at conventional doses, the average D2 occupancy was 78% (s.d. 6%). In five patients treated with the prototype atypical antipsychotic drug clozapine, a lower D2 occupancy of 48% (s.d. 11%, P less than 0.01) was found. Accordingly, clozapine is 'atypical' with respect to the striatal D2 DA receptor occupancy induced in patients. No obvious D1 DA receptor occupancy was induced by the classical neuroleptics haloperidol or sulpiride. The thioxanthene flupenthixol induced a 36-44% D1 occupancy in individual patients. In four patients treated with clozapine the D1 occupancy was 38-52%.
Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden.
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D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D003024:Clozapine