We characterized the pharmacology of N-2-methoxybenzyl-phenethylamines (NBOMes) that are novel psychoactive substances.

Abstract

Background 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.

Methods 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-HT 2A ) and 5-HT 2B 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 [TAAR 1 ], in which rat/mouse receptors were used).

Results All of the compounds potently interacted with serotonergic 5-HT 2A , 5-HT 2B , 5-HT 2C receptors and rat TAAR 1 (most K i and EC 50 : <1 μM). The N-2-methoxybenzyl substitution of 2C drugs increased the binding affinity at serotonergic 5-HT 2A , 5-HT 2C , adrenergic α 1 , dopaminergic D 1-3 , and histaminergic H 1 receptors and monoamine transporters but reduced binding to 5-HT 1A receptors and TAAR 1 . As a result, NBOMe drugs were very potent 5-HT 2A receptor agonists (EC 50 : 0.04–0.5 μM) with high 5-HT 2A /5-HT 1A selectivity and affinity for adrenergic α 1 receptors (K i : 0.3–0.9 μM) and TAAR 1 (K i : 0.06–2.2 μM), similar to LSD, but not dopaminergic D 1–3 receptors (most K i : > 1 μM), unlike LSD.