Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs).
Neuropharmacology – December 01, 2015
Source: PubMed
Summary
Many novel psychoactive substances, like NBOMe drugs, are chemically similar to phenethylamines but show surprisingly potent effects. This research meticulously mapped how these compounds bind to various brain receptors, revealing their high affinity for the 5-HT2A receptor, a key target for hallucinogens. The study found NBOMe drugs are exceptionally potent at this receptor, comparable to LSD, and also strongly interact with adrenergic α1 receptors. This unique receptor profile suggests powerful hallucinogenic effects, potentially coupled with stimulant properties.
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.