title: In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia.
abstract: Olanzapine is an atypical antipsychotic with potent antimuscarinic properties in vitro (K(i) = 2-25 nM). We studied in vivo muscarinic receptor occupancy by olanzapine at both low dose (5 mg/dy) and high dose (20 mg/dy) in several regions of cortex, striatum, thalamus and pons by analyzing [I-123]IQNB SPECT images of seven schizophrenia patients. Both low-dose and high-dose olanzapine studies revealed significantly lower [I-123]IQNB binding than that of drug-free schizophrenia patients (N = 12) in all regions except striatum. [I-123]IQNB binding was significantly lower at high-dose than low-dose in the same regions. Muscarinic occupancy by olanzapine ranged from 13% to 57% at 5 mg/dy and 26% to 79% at 20 mg/dy with an anatomical pattern indicating M(2) subtype selectivity. The [I-123]IQNB data indicate that olanzapine 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.
authors.affiliation: Clinical Brain Disorders Branch, DIRP, NIMH, 20892, Bethesda, MD 20892-1379, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Raedler
authors.forename: M B
authors.initials: MB
authors.lastname: Knable
authors.forename: D W
authors.initials: DW
authors.lastname: Jones
authors.forename: T
authors.initials: T
authors.lastname: Lafargue
authors.forename: R A
authors.initials: RA
authors.lastname: Urbina
authors.forename: M F
authors.initials: MF
authors.lastname: Egan
authors.forename: D
authors.initials: D
authors.lastname: Pickar
authors.forename: D R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism*; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D011976:Receptors, Muscarinic; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine