In Vivo Assay for Neuroleptic Receptor Binding in the Striatum

Abstract

Using PET, we investigated the potency in six patients of therapeutic doses of neuroleptic drugs for preventing specific binding of trace doses of intravenously administered 76Br-labelled bromospiperone to corpus striatum in vivo. Measured receptor occupancy showed a clear-cut dose-dependent saturation curve with increasing daily oral dose of neuroleptics, indicating the validity and reliability of the method when used as an in vivo radioreceptor assay. Following drug withdrawal in eight patients, recovery to normal or supranormal receptor availability occurred in a matter of days. The results demonstrate an approach that may help resolve controversies about, and design better strategies for, neuroleptic treatment schedules.

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride

“…With increasing dose of CP-88,059-1 there was a decrease in the binding potential (BP) of 11C-raclopride, indicating increasing central dopamine D2 receptor blockade. The results show that a single dose of between 20 and 40 mg CP-88,059-1 is likely to cause > 65% receptor occupancy -the degree associated with clinical doses of a variety of antipsychotic drugs (Cambon et al 1987;Farde et al 1988b). The correlation of the amount of CP-88,059-1 given or AUC{0-oo} of CP-88,059-1 with the PET derived measure of binding potential was greater than for the correlation with the prolactin response.…”

Clozapine can induce high dopamine D 2 receptor occupancy in vivo

“…If the kinetics of clozapine occupancy in primates reflect those in patients, this would suggest that patients receiving clozapine would show wide fluctuations in daily D 2 occupancy. On the other hand, less than 20% decrease of D 2 receptor occupancy is observed at around 24 h after a single dose of 2.0-7.5 mg haloperidol (Farde et al 1988;Nordström et al 1992), and it takes 7-12 days to return to the control level of binding after withdrawal of typical antipsychotics (Cambon et al 1987).…”

Two cases of long term dopamine D2 receptor blockade after depot neuroleptics

“…Following withdrawal of oral neuroleptics, return to normal receptor availability, as estimated by PET, is reported by Baron (1989) to occur within 5-15 days, or even within 3 days, as reported by Cambon (1987).…”