Biochemical pharmacology
February 1, 2008
Shizuo Narimatsu, Rei Yonemoto, Kazufumi Masuda et al.
The 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.
Biochemical pharmacology
April 28, 2006
Shizuo Narimatsu, Rei Yonemoto, Keita Saito et al.
The oxidative metabolism of the tryptamine 5-MeO-DIPT (Foxy) was studied in vitro using human liver microsomes and recombinant CYP enzymes. 5-MeO-DIPT was mainly converted to two metabolites: O-demethylated (5-OH-DIPT) and N-deisopropylated (5-MeO-IPT). O-demethylation showed monophasic kinetics and was almost exclusively carried out by CYP2D6, as inhibition by quinidine completely blocked this pathway. N-deisopropylation showed triphasic kinetics and involved multiple enzymes: CYP1A2, CYP2C8, CYP3A4, and to a lesser extent CYP2C9 and CYP2C19. Inhibition studies with furafylline, quercetin, sulfaphenazole, and ketoconazole suppressed N-deisopropylation by about 60%, 45%, 15%, and 40%, respectively, at 50 μM substrate. CYP2D6 is the major O-demethylase; CYP1A2, CYP2C8, and CYP3A4 are the major N-deisopropylases in human liver.