TY - JOUR
T1 - In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia
AU - Raedler, Thomas J.
AU - Knable, Michael B.
AU - Jones, Douglas W.
AU - Lafargue, Todd
AU - Urbina, Richard A.
AU - Egan, Michael F.
AU - Pickar, David
AU - Weinberger, Daniel R.
N1 - Funding Information:
From the Clinical Brain Disorders Branch (TJR, MBK, DWJ, RAU, MFE, DRW) , DIRP, NIMH, Bethesda, MD 20892; Stanley Research Foundation (MBK,), 5430 Grosvenor Lane, Suite 200, Bethesda, MD 20814; Experimental Therapeutics Branch (TL, DP), DIRP, NIMH, Bethesda, MD 20892 Address correspondence to: Daniel R. Weinberger, M.D., Chief, Clinical Brain Disorders Branch, NIMH, National Institutes of Health 10 Center Drive, 4S-235 (MSC 1379), Bethesda, MD 20892-1379, Tel.: (301) 402-7956, Fax: (301) 480-7795 E-mail: [email protected] Received June 10, 1999; revised November 19, 1999; accepted December 7, 1999.
PY - 2000/7
Y1 - 2000/7
N2 - 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.
AB - 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.
KW - Antipsychotic
KW - IQNB
KW - Muscarinic receptor
KW - Olanzapine
KW - SPECT
KW - Schizophrenia
UR - https://www.scopus.com/pages/publications/0034084299
UR - https://www.scopus.com/pages/publications/0034084299#tab=citedBy
U2 - 10.1016/S0893-133X(99)00162-1
DO - 10.1016/S0893-133X(99)00162-1
M3 - Article
C2 - 10869886
AN - SCOPUS:0034084299
SN - 0893-133X
VL - 23
SP - 56
EP - 68
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 1
ER -