Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes

Biochemical Pharmacology
S NarimatsuN Hanioka

Abstract

In vitro quantitative studies of the oxidative metabolism of (5-methoxy-N,N-diisopropyltryptamine, 5-MeO-DIPT, Foxy) were performed using human liver microsomal fractions and recombinant CYP enzymes and synthetic 5-MeO-DIPT metabolites. 5-MeO-DIPT was mainly oxidized to O-demethylated (5-OH-DIPT) and N-deisopropylated (5-MeO-IPT) metabolites in pooled human liver microsomes. In kinetic studies, 5-MeO-DIPT O-demethylation showed monophasic kinetics, whereas its N-deisopropylation showed triphasic kinetics. Among six recombinant CYP enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) expressed in yeast or insect cells, only CYP2D6 exhibited 5-MeO-DIPT O-demethylase activity, while CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP3A4 showed 5-MeO-DIPT N-deisopropylase activities. The apparent Km value of CYP2D6 was close to that for 5-MeO-DIPT O-demethylation, and the Km values of other CYP enzymes were similar to those of the low-Km (CYP2C19), intermediate-Km (CYP1A2, CYP2C8 and CYP3A4) and high-Km phases (CYP2C9), respectively, for N-deisopropylation in human liver microsomes. In inhibition studies, quinidine (1 microM), an inhibitor of CYP2D6, almost completely inhibited human liver microsomal 5-MeO-DIPT O-demethylation at a sub...Continue Reading

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Citations

Jan 2, 2016·Pharmacological Reviews·Janne T BackmanPertti J Neuvonen
Jun 15, 2011·Drug Testing and Analysis·Frank T Peters, Markus R Meyer
Feb 13, 2010·Basic & Clinical Pharmacology & Toxicology·Nobumitsu HaniokaShizuo Narimatsu
Aug 31, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Fang HeMingyi Liu
Apr 17, 2015·Archives of Toxicology·Ana Margarida AraújoMárcia Carvalho
Mar 6, 2008·The Journal of Medical Investigation : JMI·Takeshi KuwaharaYoshihiko Yamamoto
Jan 31, 2021·Molecular and Cellular Biochemistry·Zhenzhen JiangYuhui Hua

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