In Vivo Occupancy of Dopamine Receptors by Antipsychotic Drugs

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 Others^5,6 have suggested that the