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
Biochemical pharmacology February 1, 2008 DOI: 10.1016/j.bcp.2007.09.019 via PubMed
Summary
AI-generated from the abstractThe designer drug 5-MeO-DIPT (Foxy) is metabolized differently in rats than in humans. In rat liver, the main metabolic pathway is side-chain N-deisopropylation, with a smaller amount of aromatic ring O-demethylation, the opposite of human metabolism where O-demethylation dominates. Specific rat cytochrome P450 enzymes (CYP2C11, CYP3A2, CYP2D2, CYP2C6) are responsible for these reactions. Pretreatment with beta-naphthoflavone produced an additional 6-hydroxylated metabolite. These findings clarify the metabolic fate of 5-MeO-DIPT in rats, aiding toxicological studies.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat liver microsomal fractions |
| Intervention | 5-MeO-DIPT |
| Key finding | 5-MeO-DIPT is primarily metabolized by side-chain N-deisopropylation in rats, mediated by CYP2C11 and CYP3A2, with aromatic ring O-demethylation as a minor pathway mediated by CYP2D2 and CYP2C6. |
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 beta-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.