In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia

Olanzapine is an atypical antipsychotic with potent antimuscarinic properti es in vitro (K-i = 2-25 nM). We studied in vivo muscarinic receptor occupan cy by olanzapine at both low dose (5 mg/dy) and high dose (20 mg/dy) in sev eral regions of cortex, striatum, thalamus and pons by analyzing [I-123]IQN B SPECT images of seven schizophrenia patients. Both low-dose and high-dose olanzapine studies revealed significantly lower [I-123]IQNB binding than t hat of drug-free schizophrenia patients (N = 12) in all regions except stri atum. [I-123]IQNB binding was significantly lower at high-dose than low-dos e in the same regions. Muscarinic occupancy by olanzapine ranged from 13% t o 57% at 5 mg/dy and 26% to 79% at 20 mg/dy with an anatomical pattern indi cating M-2 subtype selectivity. The [I-123]IQNB data indicate that olanzapi ne is a potent and subtype-selective muscarinic antagonist in vivo, perhaps explaining its low extrapyramidal side effect profile and low incidence of anticholinergic side effects. [Neuropsychopharmacology 23:56-68, 2000] Pub lished by Elsevier Science Inc. on behalf of the American College of Neurop sychopharmacology.