4.1 Article

mRNA levels of drug-metabolizing enzymes in 11 brain regions of cynomolgus macaques

Journal

DRUG METABOLISM AND PHARMACOKINETICS
Volume 35, Issue 2, Pages 248-252

Publisher

JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.1016/j.dmpk.2019.12.003

Keywords

Brain; Cynomolgus monkey; Cytochrome P450; Drug metabolism; Tissue expression

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The cynomolgus macaque is an important nonhuman primate species in drug metabolism studies, in part because of its evolutionary closeness to humans. Cytochromes P450 (P450s) have been investigated in the major drug-metabolizing organs, i.e., the liver and small intestine, but have not been fully investigated in the brain. However, recent investigations have indicated possible important roles for P450s in the brain. In this study, by using the quantitative polymerase chain reaction, we measured the mRNA levels of 38 cynomolgus drug-metabolizing enzymes, including 19 P450s, 10 UDP-glycosyltransferases, and 9 other enzymes, in 11 brain regions. Among these drug-metabolizing enzymes, expression of 32 enzyme mRNAs were detected in one or more brain regions, indicating their possible roles in the brain. Further investigation of metabolic activities would facilitate better understanding of the importance of these enzymes in the brain. (C) 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

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