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 M2 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.
Original language | English (US) |
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Pages (from-to) | 56-68 |
Number of pages | 13 |
Journal | Neuropsychopharmacology |
Volume | 23 |
Issue number | 1 |
DOIs | |
State | Published - Jul 2000 |
Externally published | Yes |
Keywords
- Antipsychotic
- IQNB
- Muscarinic receptor
- Olanzapine
- SPECT
- Schizophrenia
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health