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Positron Emission Tomographic Analysis of Central D1 and D2 Dopamine Receptor Occupancy in Patients Treated With Classical Neuroleptics and Clozapine Relation to Extrapyramidal Side Effects

Lars Farde, MD; Anna-Lena Nordström, MD; Frits-Axel Wiesel, MD; Stefan Pauli, MD; Christer Halldin, PhD; Göran Sedvall, MD
Arch Gen Psychiatry. 1992;49(7):538-544. doi:10.1001/archpsyc.1992.01820070032005.
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• Positron emission tomography and selective radioligands were used to determine D, and D2 dopamine 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 D2 occupancy was 70% to 89%. Patients with acute extrapyramidal syndromes had a higher D2 occupancy than those without side effects. This finding indicates that neurolepticinduced extrapyramidal syndromes are related to the degree of central D2 occupancy induced in the basal ganglia. In five patients treated with clozapine, the prototype atypical antipsychotic drug, a lower D2 occupancy of 38% to 63% was found. This finding demonstrates that clozapine is also "atypical" with respect to the central D2 occupancy in patients. During treatment with clozapine, there is a low frequency of extrapyramidal syndromes, which accordingly may reflect the comparatively low D2 occupancy 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 D1 occupancy was 38% to 52%. The D, occupancy induced by clozapine and flupentixol may contribute to the antipsychotic effect of these drugs.


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