Positron Emission Tomographic Analysis of Central D1 and D2 Dopamine Receptor Occupancy in Patients Treated With Classical Neuroleptics and Clozapine

Abstract

• Positron emission tomography and selective radioligands were used to determine D_,and D₂dopamine receptor occupancy induced by neuroleptics in the basal ganglia of drug-treated schizophrenic patients. In 22 patients treated with conventional dosages of classical neuroleptics, the D₂occupancy was 70% to 89%. Patients with acute extrapyramidal syndromes had a higher D₂occupancy than those without side effects. This finding indicates that neurolepticinduced extrapyramidal syndromes are related to the degree of central D₂occupancy induced in the basal ganglia. In five patients treated with clozapine, the prototype atypical antipsychotic drug, a lower D₂occupancy of 38% to 63% was found. This finding demonstrates that clozapine is also "atypical" with respect to the central D₂occupancy in patients. During treatment with clozapine, there is a low frequency of extrapyramidal syndromes, which accordingly may reflect the comparatively low D₂occupancy induced by clinical doses of clozapine. Classical neuroleptics, like haloperidol or sulpiride, did not cause any evident D_,occupancy, but the thioxanthene flupentixol induced a 36% to 44% occupancy. In four patients treated with clozapine, the D₁occupancy was 38% to 52%. The D_,occupancy induced by clozapine and flupentixol may contribute to the antipsychotic effect of these drugs.