Regioselective biotransformation of CNS drugs and its clinical impact on adverse drug reactions

Expert Opinion on Drug Metabolism & Toxicology
Yin Cheong WongZhong Zuo

Abstract

Adverse drug reactions (ADRs) continue to be one of the major causes of failure in drug development while limiting the clinical utilities of many drugs. Contribution of the metabolites formed in vivo to ADRs could be more significant than we might have expected. This review focuses on the relationship between regioselectivity in biotransformation and the ADRs of drugs acting on the central nervous system (CNS). "Regioselectivity" is defined as an exclusively or significantly preferential metabolic reaction at one (or several) site(s) on the substrate molecule. Several CNS drugs and toxicants, of which the metabolites play pivotal roles in ADRs, are summarized in details with the highlight on the roles of metabolism in both toxification and detoxification. The article also discusses in silico predictions of regioselectivity and the formation of toxic metabolites which are becoming increasingly important. Researchers working on CNS drugs face particular challenges in predicting drug metabolism and potential toxicities of their metabolites. A number of factors contribute to the difficulty of accurate prediction of metabolite disposition in the human brain. Better knowledge of regioselectivity in biotransformation and elucidation o...Continue Reading

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Citations

Sep 12, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Sophia Yui Kau FongZhong Zuo
Dec 18, 2013·Expert Opinion on Drug Metabolism & Toxicology·Sophia Yui Kau FongZhong Zuo
Apr 9, 2014·International Journal of Pharmaceutics·Shuai QianZhong Zuo
Aug 25, 2012·Journal of Chemical Information and Modeling·Valérie Campagna-SlaterNicolas Moitessier

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