25CN-NBOMe Metabolites in Rat Urine, Human Liver Microsomes and C. elegans—Structure Determination and Synthesis of the Most Abundant Metabolites
Anna Šuláková, Jitka Nykodemová, Petr Palivec, Radek Jurok, Silvie Rimpelová, Tereza Leonhardt, Klára Šíchová, Tomáš Páleníček, Martin Kuchař
Metabolites March 31, 2021 DOI: 10.3390/metabo11040212 via OpenAlex
Summary
N-Benzylphenethylamines, including 25CN-NBOMe, are novel psychedelic substances with limited metabolism data. This study investigated the metabolic profile of 25CN-NBOMe in rats in vivo and in human liver microsomes and Cunninghamella elegans mycelium in vitro. Major metabolic pathways include mono- and bis-O-demethylation, hydroxylation, and combinations, followed by glucuronidation, sulfation, or N-acetylation of primary metabolites. The cyano group was either hydrolyzed to an amide or carboxylic acid or remained unchanged. Differences between species should be considered in metabolism studies of novel substances.
Study at a glance
| Characteristics | In vivo and in vitro metabolism study Peer reviewed |
|---|---|
| Population | Rats, human liver microsomes, and Cunninghamella elegans mycelium |
| Intervention | 25CN-NBOMe |
| Keywords | Glucuronidation Metabolism Sulfation Metabolic pathway Hydroxylation |
| Citations | 11 |
| Key finding | Major metabolic pathways of 25CN-NBOMe include mono- and bis-O-demethylation, hydroxylation, and combinations, followed by glucuronidation, sulfation, or N-acetylation, with the cyano group either hydrolyzed or unchanged. |
Abstract
N-Benzylphenethylamines are novel psychedelic substances increasingly used for research, diagnostic, or recreational purposes. To date, only a few metabolism studies have been conducted for N-2-methoxybenzylated compounds (NBOMes). Thus, the available 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe) metabolism data are limited. Herein, we investigated the metabolic profile of 25CN-NBOMe in vivo in rats and in vitro in Cunninghamella elegans (C. elegans) mycelium and human liver microsomes. Phase I and phase II metabolites were first detected in an untargeted screening, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of the most abundant metabolites by comparison with in-house synthesized reference materials. The major metabolic pathways described within this study (mono- and bis-O-demethylation, hydroxylation at different positions, and combinations thereof, followed by the glucuronidation, sulfation, and/or N-acetylation of primary metabolites) generally correspond to the results of previously reported metabolism of several other NBOMes. The cyano functional group was either hydrolyzed to the respective amide or carboxylic acid or remained untouched. Differences between species should be taken into account in studies of the metabolism of novel substances.