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

TLDR

Positron emission tomography with selective radioligands quantified D1 and D2 dopamine receptor occupancy in the basal ganglia of schizophrenic patients receiving neuroleptics. Classical neuroleptics produced 70–89 % D2 occupancy and were associated with higher extrapyramidal symptoms, whereas clozapine yielded 38–63 % D2 occupancy (and 38–52 % D1 occupancy) with fewer extrapyramidal side effects, suggesting that lower D2 occupancy contributes to its atypical profile.

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.