2011 CCNP Heinz Lehmann Award paper: Cytochrome P450–mediated drug metabolism in the brain
Identifieur interne : 000E82 ( Main/Exploration ); précédent : 000E81; suivant : 000E832011 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.
English descriptors
- KwdEn :
- Animals, Brain (enzymology), Central Nervous System Agents (metabolism), Central Nervous System Agents (pharmacology), Cytochrome P-450 Enzyme System (metabolism), Haplorhini, Humans, Organ Specificity (physiology), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (enzymology), Rats, Smoking (metabolism), Species Specificity, Substance Withdrawal Syndrome (enzymology), Tobacco Use Disorder (enzymology), Tobacco Use Disorder (genetics).
- MESH :
- chemical , metabolism : Central Nervous System Agents, Cytochrome P-450 Enzyme System.
- chemically induced : Parkinson Disease, Secondary.
- enzymology : Brain, Parkinson Disease, Secondary, Substance Withdrawal Syndrome, Tobacco Use Disorder.
- genetics : Tobacco Use Disorder.
- metabolism : Smoking.
- chemical , pharmacology : Central Nervous System Agents.
- physiology : Organ Specificity.
- Animals, Haplorhini, Humans, Rats, Species Specificity.
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
Affiliations:
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Le document en format XML
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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><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (enzymology)</term><term>Central Nervous System Agents (metabolism)</term><term>Central Nervous System Agents (pharmacology)</term><term>Cytochrome P-450 Enzyme System (metabolism)</term><term>Haplorhini</term><term>Humans</term><term>Organ Specificity (physiology)</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (enzymology)</term><term>Rats</term><term>Smoking (metabolism)</term><term>Species Specificity</term><term>Substance Withdrawal Syndrome (enzymology)</term><term>Tobacco Use Disorder (enzymology)</term><term>Tobacco Use Disorder (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Central Nervous System Agents</term><term>Cytochrome P-450 Enzyme System</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term><term>Parkinson Disease, Secondary</term><term>Substance Withdrawal Syndrome</term><term>Tobacco Use Disorder</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Tobacco Use Disorder</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Smoking</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Central Nervous System Agents</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Organ Specificity</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Haplorhini</term><term>Humans</term><term>Rats</term><term>Species Specificity</term></keywords></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><affiliations><list></list><tree><noCountry><name sortKey="Miksys, Sharon" sort="Miksys, Sharon" uniqKey="Miksys S" first="Sharon" last="Miksys">Sharon Miksys</name><name sortKey="Tyndale, Rachel F" sort="Tyndale, Rachel F" uniqKey="Tyndale R" first="Rachel F." last="Tyndale">Rachel F. Tyndale</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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