Related Experiment Video
Updated: May 16, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Cytochrome P450-mediated drug metabolism in the brain
Sharon Miksys1, Rachel F Tyndale
1The Centre for Addiction and Mental Health, Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ont.
Abstract:
Cytochrome P450 enzymes (CYPs) metabolize many drugs that act on the central nervous system (CNS), such as antidepressants and antipsychotics; drugs of abuse; endogenous neurochemicals, such as serotonin and dopamine; neurotoxins; and carcinogens. This takes place primarily in the liver, but metabolism can also occur in extrahepatic organs, including the brain. This is important for CNS-acting drugs, as variation in brain CYP-mediated metabolism may be a contributing factor when plasma levels do not predict drug response. This review summarizes the characterization of CYPs in the brain, using examples from the CYP2 subfamily, and discusses sources of variation in brain CYP levels and metabolism. Some recent experiments are described that demonstrate how changes in brain CYP metabolism can influence drug response, toxicity and drug-induced behaviours. Advancing knowledge of brain CYP-mediated metabolism may help us understand why patients respond differently to drugs used in psychiatry and predict risk for psychiatric disorders, including neurodegenerative diseases and substance abuse.
Related Concept Videos
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs
The drug's acidity or basicity is essential in determining the metabolic...
Drug Metabolism: Phase I Reactions
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Pharmacogenetics of Drug Metabolism: Overview
Factors Affecting Drug Biotransformation: Biological
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
