DARK Classics in Chemical Neuroscience: NBOMes

Abstract

N-Benzylphenethylamines, commonly known as NBOMes, are synthetic psychedelic compounds derived from the phenethylamine class of psychedelics (2C-X compounds), which originally have been derived from the naturally occurring alkaloid mescaline. Analogously to their parent compounds and other classical psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), NBOMes are believed to exert their main pharmacological effects through activation of serotonin 2A (5-HT_2A) receptors. Since their introduction as New Psychoactive Substances (NPSs) in 2010, NBOMes have been widely used for recreational purposes; this has resulted in numerous cases of acute toxicity, sometimes with lethal outcomes, leading to the classification of several NBOMes as Schedule I substances in 2013. However, in addition to their recreational use, the NBOMe class has yielded several important biochemical tools, including [¹¹C]Cimbi-36, which is now being used in positron emission tomography (PET) studies of the 5-HT_2A and 5-HT_2C receptors in the mammalian brain, and 25CN-NBOH, one of the most selective 5-HT_2A receptor agonists developed to date. In this Review, the history, chemistry, structure-activity relationships, ADME (absorption, distribution, metabolism, and excretion) properties, and safety profiles of NBOMes will be outlined and discussed.

Keywords: 5-HT2A receptor; N-Benzylphenethylamines; novel psychoactive substance; psychedelics.

Figure 1.

Overview and classification of the chemical scaffolds considered as classical hallucinogens. The core scaffolds are highlighted in red.

Figure 2.

Overview of the structure–activity relationship of NBOMes at the 5-HT_2AR.

Figure 3.

Chemical structures of DMBMPP and 25CN-NBOH.

Scheme 1.

Evolution of the Phenethylamine Scaffold, from Mescaline to 25B-NBOMe

Scheme 2.. Synthesis of NBOMes, Exemplified by the Synthesis of 25B-NBOMe via 2C-B^–a

^aReagents and conditions: (i) CH₃NO₂, NH₄OH, 70 °C, 2 h, quant; (ii) H₂, Pd/C, MeOH, r.t., 1 h, 99%; (iii) Br₂, AcOH, r.t., 16 h, 99%; (iv) 2-methoxybenzaldehyde, Et₃N, EtOH, reflux, 3 h, followed by NaBH₄, r.t., 30 min, 85%.

Scheme 3.

Putative Phase I Metabolic Pathways for 25B-NBOMe in Humans