Cytochrome P450―mediated drug metabolism in the brain

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 metabol...

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Bibliographic Details
Published in:Journal of psychiatry & neuroscience 2013-05, Vol.38 (3), p.152-163
Main Authors: MIKSYS, Sharon, TYNDALE, Rachel F
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - enzymology
Central Nervous System Agents - metabolism
Central Nervous System Agents - pharmacology
Cytochrome P-450 Enzyme System - metabolism
Fundamental and applied biological sciences. Psychology
Haplorhini
Humans
Medical sciences
Organ Specificity - physiology
Parkinson Disease, Secondary - chemically induced
Parkinson Disease, Secondary - enzymology
Psychoanalysis
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Rats
Smoking - metabolism
Species Specificity
Substance Withdrawal Syndrome - enzymology
Tobacco Use Disorder - enzymology
Tobacco Use Disorder - genetics
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Description
Summary: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.
ISSN:1180-4882
1488-2434
DOI:10.1503/jpn.120133