Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs).

NBOMe drugs, a class of novel psychoactive substances, bind strongly to serotonin receptors (5-HT2A, 5-HT2B, 5-HT2C) and rat trace amine-associated receptor-1, with most affinities and potencies below 1 μM, similar to LSD. Unlike LSD, NBOMe drugs also interact with α1 receptors, suggesting they may produce hallucinogenic effects comparable to LSD but with additional stimulant properties. The study characterized the receptor binding profiles of twelve 2C drugs, their NBOMe analogs, and LSD in human cells expressing human receptors or transporters, except for TAAR1 where rat/mouse receptors were used.

Study at a glance

Abstract

N-2-methoxybenzyl-phenethylamines (NBOMe drugs) are newly used psychoactive substances with poorly defined pharmacological properties. The aim of the present study was to characterize the receptor binding profiles of a series of NBOMe drugs compared with their 2,5-dimethoxy-phenethylamine analogs (2C drugs) and lysergic acid diethylamide (LSD) in vitro. We investigated the binding affinities of 2C drugs (2C-B, 2C-C, 2C-D, 2C-E, 2C-H, 2C-I, 2C-N, 2C-P, 2C-T-2, 2C-T-4, 2C-T-7, and mescaline), their NBOMe analogs, and LSD at monoamine receptors and determined functional 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2B receptor activation. Binding at and the inhibition of monoamine uptake transporters were also determined. Human cells that were transfected with the respective human receptors or transporters were used (with the exception of trace amine-associated receptor-1 [TAAR1], in which rat/mouse receptors were used). All of the compounds potently interacted with serotonergic 5-HT2A, 5-HT2B, 5-HT2C receptors and rat TAAR1 (most Ki and EC50: 1 μM), unlike LSD. The binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α1 receptor interactions.