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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat liver microsomal fractions |
| Intervention | 5-MeO-DIPT |
| Topics | 5-MeO-DMT |
| Key findings | 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.
Comparable studies
Other experimental studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom | 1994 | Experimental study | |
| Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers | 2019 | Within-subjects experimental study | n = 11 |
| Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats | 1990 | Experimental study | n = 10 |
| Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide | 1962 | Experimental study |
Citations in the library
Cited by 5
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Metabolism of designer drugs of abuse: an updated review. Current Drug Metabolism June 1, 2010
- Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions The AAPS Journal May 3, 2008
- Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics. Biochemical Pharmacology July 1, 2010
- A systematic study of changes in monoamine neurotransmitters in the rat brain following acute administration of alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT). Neuroscience Research July 1, 2025
Cites 7
- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- A foxy intoxication. Forensic Science International February 10, 2005
- Foxy, a designer tryptamine hallucinogen. Journal of Analytical Toxicology 2003
- 5-Methoxy-N,N-diisopropyltryptamine (Foxy), a selective and high affinity inhibitor of serotonin transporter. Toxicology Letters April 5, 2007
and 2 more in the library