Movement disorders in schizophrenia and implications for the use of newer antipsychotics

Abstract

Olanzapine is a new antipsychotic drug with affinity for 5-HT2, D2, D1, and muscarinic receptors. Positron emission tomography and the radioligands [11C]raclopride and [11C]NMSP were used to measure D2 and 5-HT2 receptor occupancy in three healthy subjects after 10 mg olanzapine orally. After seven hours D2 receptor occupancy was 63%, 62% and 59%, respectively. After 9.5 hours 5-HT2 receptor occupancy was 74%, 86% and 92%. D2 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 D2 and 5-HT2 receptor occupancy should be similar to that induced by standard doses of clozapine. Detailed evaluation of the doseresponse characteristics of olanzapine and direct clinical comparison to clozapine will thus provide valuable leads to the clarification of atypical antipsychotic action.