A PET study of 5-HT2 and D2 dopamine receptor occupancy induced by olanzapine in healthy subjects.
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 dose-response characteristics of olanzapine and direct clinical comparison to clozapine will thus provide valuable leads to the clarification of atypical antipsychotic action.
Nyberg
S
S
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Farde
L
L
Halldin
C
C
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D001569:Benzodiazepines; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine