The role of human hepatic cytochrome P450 isozymes in the metabolism of racemic 3,4-methylenedioxy-methamphetamine and its enantiomers

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Markus R MeyerHans H Maurer

Abstract

The entactogen, 3,4-methylenedioxy-methamphetamine (MDMA), is a chiral drug that is mainly metabolized by N-demethylation and demethylenation. The involvement of cytochrome P450 (P450) isozymes in these metabolic steps has been studied by inhibition assays with human liver microsomes and, in part, with heterologously expressed human P450 isozymes. However, a comprehensive study on the involvement of all relevant human P450s has not been published yet. In addition, the chirality of this drug was not considered in these in vitro studies. The aim of the present work was to study the contribution of human P450 isozymes in the N-demethylation and demethylenation of racemic MDMA and its single enantiomers. MDMA and its enantiomers were incubated using heterologously expressed human P450s, and the metabolites were quantified by gas chromatography-mass spectrometry after derivatization with S-heptafluorobutyrylprolyl chloride. The highest contribution for the N-demethylation as calculated from the enzyme kinetic data, were obtained for CYP2B6 (R,S-MDMA), CYP1A2 (R-MDMA), and CYP2B6 (S-MDMA). In the case of the demethylenation, the isozyme with the highest contribution to net clearance for R,S-MDMA, R-MDMA, and S-MDMA was CYP2D6. For th...Continue Reading

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Citations

Feb 3, 2009·Analytical and Bioanalytical Chemistry·Melanie MuellerHans H Maurer
Apr 3, 2010·Journal of Computer-aided Molecular Design·Rayomand J UnwallaChristine Humblet
Apr 18, 2009·Molecular Neurobiology·João Paulo CapelaFélix Carvalho
Dec 18, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Annmarie Ramkissoon, Peter G Wells
Jul 25, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Melanie MuellerGeorge A Ricaurte
Nov 16, 2013·Analytical and Bioanalytical Chemistry·Rebecca L HartmanMarilyn A Huestis
Dec 14, 2011·The Veterinary Quarterly·Irene Antolino-LoboMajorie B M van Duursen
Jul 6, 2010·European Journal of Pharmacology·Jalal PourahmadAli Reza Khajeamiri
Jun 15, 2011·Drug Testing and Analysis·Frank T Peters, Markus R Meyer
Mar 18, 2010·British Journal of Clinical Pharmacology·Linghui LiJohn Mendelson
Nov 12, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C DowneyK M O'Boyle
Jan 25, 2017·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Patrick VizeliMatthias E Liechti
Dec 19, 2017·Psychopharmacology·Elizabeth G PittsLeonard L Howell
Aug 5, 2010·Therapeutic Drug Monitoring·Hans H Maurer
Aug 26, 2011·Analytical and Bioanalytical Chemistry·Markus R Meyer, Hans H Maurer
Oct 23, 2010·Drug Testing and Analysis·James P ScarthTiia Kuuranne
Mar 21, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Markus R MeyerHans H Maurer
Sep 24, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrea E SteuerThomas Kraemer
Apr 15, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Irene Antolino-LoboMajorie B M van Duursen
Aug 9, 2017·Scientific Reports·Hisashi TakedaTomoo Hosoe
Oct 24, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·John T Rodgers, Jeffrey P Jones
Jul 14, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Su Min ChoiSangkyu Lee

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