This in vitro study investigates the receptor binding profiles of NBOMe drugs compared to their 2C drug analogs and LSD. It finds that NBOMe drugs exhibit high affinity for 5-HT2A receptors, suggesting strong hallucinogenic effects similar to LSD, but with potentially more stimulant properties due to interactions with α1 receptors.
Abstract of Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)
“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-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).
Results: All of the compounds potently interacted with serotonergic 5-HT2A, 5-HT2B, 5-HT2C receptors and rat TAAR1 (most Ki and EC50: <1 μM). The N-2-methoxybenzyl substitution of 2C drugs increased the binding affinity at serotonergic 5-HT2A, 5-HT2C, adrenergic α1, dopaminergic D1-3, and histaminergic H1 receptors and monoamine transporters but reduced binding to 5-HT1A receptors and TAAR1. As a result, NBOMe drugs were very potent 5-HT2A receptor agonists (EC50: 0.04–0.5 μM) with high 5-HT2A/5-HT1A selectivity and affinity for adrenergic α1 receptors (Ki: 0.3–0.9 μM) and TAAR1 (Ki: 0.06–2.2 μM), similar to LSD, but not dopaminergic D1–3 receptors (most Ki: > 1 μM), unlike LSD.
Conclusion: The binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α1 receptor interactions.”
Authors: Anna Rickli, Dino Luethi, Julian Reinisch, Danièle Buchy, Marius C. Hoener & Matthias E. Liechti
Summary of Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)
The aim of the study was to compare the receptor binding profiles of NBOMe drugs with their 2,5-dimethoxyphenethylamine analogs and lysergic acid diethylamide.
We investigated the binding affinities of 2C drugs, their NBOMe analogs, and LSD at monoamine receptors and determined functional 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2B receptor activation. The NBOMe drugs were very potent 5-HT2A receptor agonists but reduced binding to 5-HT 1A receptors and TAAR1.
New psychoactive substances are constantly emerging on the illicit drug market and typically sold via the Internet. N-2-methoxybenzyl-phenethylamines are very potent 5-HT2A receptor agonists with strong hallucinogenic properties in animals and humans. NBOMe drugs have been reported to produce psycho- and cardiovascular stimulant effects, in addition to hallucinations, and have been found to inhibit the norepinephrine and serotonin transporters, similar to amphetamines, although with only very low potency.
Find this paper
https://doi.org/10.1016/j.neuropharm.2015.08.034
Paywall | Google Scholar | Backup | 🕊
Cite this paper (APA)
Rickli, A., Luethi, D., Reinisch, J., Buchy, D., Hoener, M. C., & Liechti, M. E. (2015). Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2, 5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology, 99, 546-553.
Study details
Compounds studied
2C-X
Topics studied
Chemistry
Neuroscience
Safety
Addiction
Study characteristics
Bio/Neuro
?>