2011 CCNP Heinz Lehmann Award paper: Cytochrome P450–mediated drug metabolism in the brain
Identifieur interne : 000B86 ( Pmc/Curation ); précédent : 000B85; suivant : 000B872011 CCNP Heinz Lehmann Award paper: Cytochrome P450–mediated drug metabolism in the brain
Auteurs : Sharon Miksys ; Rachel F. TyndaleSource :
- Journal of Psychiatry & Neuroscience : JPN [ 1180-4882 ] ; 2013.
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.
Url:
DOI: 10.1503/jpn.120133
PubMed: 23199531
PubMed Central: 3633708
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">2011 CCNP Heinz Lehmann Award paper: Cytochrome P450–mediated drug metabolism in the brain</title><author><name sortKey="Miksys, Sharon" sort="Miksys, Sharon" uniqKey="Miksys S" first="Sharon" last="Miksys">Sharon Miksys</name></author><author><name sortKey="Tyndale, Rachel F" sort="Tyndale, Rachel F" uniqKey="Tyndale R" first="Rachel F." last="Tyndale">Rachel F. Tyndale</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23199531</idno><idno type="pmc">3633708</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633708</idno><idno type="RBID">PMC:3633708</idno><idno type="doi">10.1503/jpn.120133</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000B86</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B86</idno><idno type="wicri:Area/Pmc/Curation">000B86</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B86</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">2011 CCNP Heinz Lehmann Award paper: Cytochrome P450–mediated drug metabolism in the brain</title><author><name sortKey="Miksys, Sharon" sort="Miksys, Sharon" uniqKey="Miksys S" first="Sharon" last="Miksys">Sharon Miksys</name></author><author><name sortKey="Tyndale, Rachel F" sort="Tyndale, Rachel F" uniqKey="Tyndale R" first="Rachel F." last="Tyndale">Rachel F. Tyndale</name></author></analytic><series><title level="j">Journal of Psychiatry & Neuroscience : JPN</title><idno type="ISSN">1180-4882</idno><idno type="eISSN">1488-2434</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front></TEI><pmc article-type="review-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Psychiatry Neurosci</journal-id><journal-id journal-id-type="iso-abbrev">J Psychiatry Neurosci</journal-id><journal-title-group><journal-title>Journal of Psychiatry & Neuroscience : JPN</journal-title></journal-title-group><issn pub-type="ppub">1180-4882</issn><issn pub-type="epub">1488-2434</issn><publisher><publisher-name>Canadian Medical Association</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23199531</article-id><article-id pub-id-type="pmc">3633708</article-id><article-id pub-id-type="doi">10.1503/jpn.120133</article-id><article-id pub-id-type="publisher-id">jpn-38-152</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>2011 CCNP Heinz Lehmann Award paper: Cytochrome P450–mediated drug metabolism in the brain</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Miksys</surname><given-names>Sharon</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Tyndale</surname><given-names>Rachel F.</given-names></name><degrees>PhD</degrees><xref ref-type="corresp" rid="c1-jpn-38-152"></xref></contrib><aff id="af1-jpn-38-152">Centre for Addiction and Mental Health, Departments of Pharmacology and Toxicology and Psychiatry, University of Toronto, Toronto, Ont., Canada</aff></contrib-group><author-notes><corresp id="c1-jpn-38-152">Correspondence to: R.F. Tyndale, Department of Pharmacology and Toxicology, 1 King’s College Circle, Toronto ON M5S 1A8; <email>r.tyndale@utoronto.ca</email></corresp></author-notes><pub-date pub-type="ppub"><month>5</month><year>2013</year></pub-date><volume>38</volume><issue>3</issue><fpage>152</fpage><lpage>163</lpage><history><date date-type="received"><day>16</day><month>7</month><year>2012</year></date><date date-type="rev-recd"><day>22</day><month>10</month><year>2012</year></date><date date-type="accepted"><day>25</day><month>10</month><year>2012</year></date></history><permissions><copyright-statement>© 2013 Canadian Medical Association</copyright-statement><copyright-year>2013</copyright-year></permissions><abstract><p>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.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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