Oxidation of 5-methoxy-N,N-diisopropyltryptamine in rat liver microsomes and recombinant cytochrome P450 enzymes

Shizuo Narimatsu, Rei Yonemoto, Kazufumi Masuda, Takashi Katsu, Masato Asanuma, Tooru Kamata, Munehiro Katagi, Hitoshi Tsuchihashi, Takuya Kumamoto, Tsutomu Ishikawa, Shinsaku Naito, Shigeru Yamano, Nobumitsu Hanioka

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17 Citations (Scopus)

Abstract

The oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a tryptamine-type designer drug, was studied using rat liver microsomal fractions and recombinant cytochrome P450 (CYP) enzymes. 5-MeO-DIPT was biotransformed mainly into a side-chain N-deisopropylated metabolite and partially into an aromatic ring O-demethylated metabolite in liver microsomal fractions from untreated rats of both sexes. This metabolic profile is different from our previous findings in human liver microsomal fractions, in which the aromatic ring O-demethylation was the major pathway whereas the side-chain N-deisopropylation was minor [Narimatsu S, Yonemoto R, Saito K, Takaya K, Kumamoto T, Ishikawa T, et al. Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes. Biochem Pharmacol 2006;71:1377-85]. Kinetic and inhibition studies indicated that the side-chain N-dealkylation is mediated by CYP2C11 and CYP3A2, whereas the aromatic ring O-demethylation is mediated by CYP2D2 and CYP2C6 in untreated male rats. Pretreatment of male rats with β-naphthoflavone (BNF) produced an aromatic ring 6-hydroxylated metabolite. Recombinant rat and human CYP1A1 efficiently catalyzed 5-MeO-DIPT 6-hydroxylation under the conditions used. These results provide valuable information on the metabolic fate of 5-MeO-DIPT in rats that can be used in the toxicological study of this designer drug.

Original languageEnglish
Pages (from-to)752-760
Number of pages9
JournalBiochemical Pharmacology
Volume75
Issue number3
DOIs
Publication statusPublished - Feb 1 2008

Keywords

  • 5-Methoxy-N,N-diisopropyltryptamine
  • 6-Hydroxylation
  • CYP1A1
  • CYP2C11
  • CYP2D2
  • CYP3A2
  • N-Deisopropylation
  • O-Demethylation
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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    Narimatsu, S., Yonemoto, R., Masuda, K., Katsu, T., Asanuma, M., Kamata, T., Katagi, M., Tsuchihashi, H., Kumamoto, T., Ishikawa, T., Naito, S., Yamano, S., & Hanioka, N. (2008). Oxidation of 5-methoxy-N,N-diisopropyltryptamine in rat liver microsomes and recombinant cytochrome P450 enzymes. Biochemical Pharmacology, 75(3), 752-760. https://doi.org/10.1016/j.bcp.2007.09.019