Document Detail


Cytochrome P450-mediated drug metabolism in the brain.
MedLine Citation:
PMID:  23199531     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Sharon Miksys; Rachel F Tyndale
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  Journal of psychiatry & neuroscience : JPN     Volume:  37     ISSN:  1488-2434     ISO Abbreviation:  J Psychiatry Neurosci     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107859     Medline TA:  J Psychiatry Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  120133     Citation Subset:  -    
Affiliation:
The Centre for Addiction and Mental Health, Departments of Pharmacology and Toxicology and Psychiatry, University of Toronto, Toronto, Ont.
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