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May 1989

Dopamine Receptor Occupancy and Plasma Haloperidol Levels-Reply

Arch Gen Psychiatry. 1989;46(5):483-484. doi:10.1001/archpsyc.1989.01810050097022

In Reply.—  Our finding of a 65% to 85% D2-dopamine receptor occupancy in schizophrenic patients treated with chemically distinct antipsychotic drugs represents strong support for the hypothesis that the antipsychotic effect is mediated by blockade of D2-dopamine receptors.1 The theoretically expected curvilinear relationship between neuroleptic drug concentration in plasma and D2-dopamine receptor occupancy has now been confirmed in several PET studies of patients receiving neuroleptic therapy.1,2 However, caution must be exercised before accepting the conclusions reached by Wolkin et al regarding the clinical utility of plasma levels.In their letter, Wolkin et al comment on their curve between plasma haloperidol levels and receptor occupancy: "The lack of scatter about the curve implies a close relationship between plasma level and receptor blockade. This is a strong argument for the clinical utility of plasma neuroleptic drug levels."Despite a large number of studies, a generally confirmed relationship between plasma drug concentrations