MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?
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- dc.contributor.author Torre Fornell, Rafael de laca
- dc.contributor.author Yubero Lahoz, Samanta, 1985-ca
- dc.contributor.author Pardo Lozano, Ricardoca
- dc.contributor.author Farré Albaladejo, Magíca
- dc.date.accessioned 2015-06-08T08:49:53Z
- dc.date.available 2015-06-08T08:49:53Z
- dc.date.issued 2012ca
- dc.description.abstract In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI) of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer (PM) phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.Yubero-Lahoz S, Pardo-Lozano R, Farré Men
- dc.format.mimetype application/pdfca
- dc.identifier.citation de la Torre R, Yubero-Lahoz S, Pardo-Lozano R, Farré M. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant? Front Genet. 2012;3:235. DOI: 10.3389/fgene.2012.00235ca
- dc.identifier.doi http://dx.doi.org/10.3389/fgene.2012.00235
- dc.identifier.issn 1664-8021ca
- dc.identifier.uri http://hdl.handle.net/10230/23759
- dc.language.iso engca
- dc.publisher Frontiersca
- dc.relation.ispartof Frontiers in Genetics. 2012;3:235
- dc.rights © 2012 de la Torre, Yubero-Lahoz, Pardo-Lozano and Farré. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.en
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by/3.0/
- dc.subject.keyword MDMAen
- dc.subject.keyword CYP2D6en
- dc.subject.keyword Methamphetamineen
- dc.subject.keyword Pharmacogeneticsen
- dc.subject.keyword Ecstasyen
- dc.subject.other MDMA (Droga) -- Farmacocinèticaca
- dc.subject.other MDMA (Droga) -- Metabolismeca
- dc.subject.other Medicaments -- Interaccióca
- dc.title MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?en
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca