Journal Article

Saturation of striatal D<sub>2</sub> dopamine receptors by clozapine

Svante Nyberg, Yuan-Hwa Chou and Christer Halldin

in International Journal of Neuropsychopharmacology

Published on behalf of International College of Neuropsychopharmacology

Volume 5, issue 1, pages 11-16
Published in print March 2002 | ISSN: 1461-1457
Published online March 2002 | e-ISSN: 1469-5111 | DOI: http://dx.doi.org/10.1017/S1461145701002693
Saturation of striatal D2 dopamine receptors by clozapine

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Abstract

Positron emission tomography (PET) studies have demonstrated low striatal D2 dopamine receptor occupancy in clozapine-treated schizophrenic patients. The aim of this pilot study was to explore if this low receptor occupancy indeed represents partial saturability of striatal D2 dopamine receptors by clozapine. Three anaesthetized Cynomolgus monkeys were examined during one day with PET and [11C]raclopride at baseline and after intravenous injections of clozapine 1.5 mg/kg followed by 18.5 mg/kg. The estimated corresponding human oral doses were approx. 210 mg/d and 2800 mg/d. D2 dopamine receptor occupancy was calculated using an equilibrium-ratio analysis and ranged from 54 to 58% after 1·5 mg/kg and 87 to 89% after the total dose 20 mg/kg. The calculated maximal occupancy was 93%. We conclude that PET-measured D2 dopamine receptor occupancy by clozapine can be described using a model based on the law of mass action, previously validated for conventional antipsychotics. Therefore, sufficiently high doses of clozapine are expected to produce complete striatal D2 dopamine receptor occupancy. The findings further support our previous findings of low D2 dopamine receptor occupancy in patients treated with standard doses of clozapine.

Keywords: Clozapine; D2 dopamine receptor; positron emission tomography; [11C]raclopide

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