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In Vivo Occupancy of Dopamine Receptors by Antipsychotic Drugs

Herbert Y. Meltzer, MD; Craig A. Stockmeier, PhD
Arch Gen Psychiatry. 1992;49(7):588-589. doi:10.1001/archpsyc.1992.01820070082019.
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To the Editor. —  Clozapine hydrochloride, an atypical antipsychotic drug, has been reported to occupy fewer striatal D2 dopamine receptors (DRD2) (38% to 63%) than typical neuroleptic drugs (>70%), as determined by positron emission tomography (PET) using raclopride labeled with carbon 11.1-3 Furthermore, clozapine has been shown by PET studies using 11CSchering 23390 as ligand to occupy more D1 dopamine receptors (DRD1) than typical neuroleptics.2,3See also p 538.Decreased DRD2 and increased DRD1 occupancy has been suggested as the explanation of why clozapine does not produce extrapyramidal symptoms in humans.3 We have offered an alternative theory, namely, that clozapine produces fewer extrapyramidal symptoms because of its higher serotonin2 (5-HT2) receptor-blocking properties compared with its DRD2-blocking properties.4 We have also suggested that the latter mechanism is relevant to the antipsychotic advantages of clozapine.5 Others5,6 have suggested that the

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