A PET study of 5-HT2 and D-2 dopamine receptor occupancy induced by olanzapine in healthy subjects

Olanzapine is a new antipsychotic drug with affinity for 5-HT2, D-2, D-1, and muscarinic receptors. Positron emission tomography and the radioligands [C-11]raclopride and [C-11]raclopride and [C-11]NSMP were used to measure D-2 and 5-HT2 receptor occupancy in three healthy subjects after 10 mg olanzapine orally. After seven hours D-2 receptor occupancy was 63%, 62% and 59%, respectively. After 9.5 hours 5-HT2 receptor occupancy was 74%, 86% and 92%. D-2 and 5-HT2 receptor occupancy was comparable to that found in patients continuously treated with clozapine. Clinical efficacy has been demonstrated for olanzapine in the dose range 5 to 15 mg per day. Extrapolation from our present observations after a 10 mg single-dose suggest, that at the lower end of the clinically examined dose range the D-2 and 5-HT2 receptor occupancy should be similar to that induced by standard doses of clozapine. Detailed evaluation of the dose-response characteristics of olanzapine and direct clinical comparison to clozapine will thus provide valuable leads to the clarification of atypical antipsychotic action. (C) 1997 American College of Neuropsychopharmacology.