Archives of toxicology
May 1, 2023
Marie H Deventer, Mattias Persson, Antonio Laus et al.
7 citations
Some psychedelic substances that carry the N-benzyl phenethylamine (NBOMe) structure can activate the µ opioid receptor (MOR), an off-target effect confirmed by two different assays. This activation was blocked by the opioid antagonist naloxone, indicating these NBOMes bind to the same opioid binding pocket as conventional opioids. Molecular docking showed plausible interactions of 25I-NBOMe with MOR similar to those of opioids. However, MOR activation occurred only at high concentrations, making relevant opioid toxicity in vivo unlikely at physiologically relevant levels. Small modifications to the NBOMe structure could yield more potent MOR agonists with dual MOR/5-HT2A activation potential.
British journal of pharmacology
July 14, 2026
Darta Stalberga, Robert Kronstrand, Bianca Schranz et al.
Synthetic cathinones, a large class of new psychoactive substances, primarily inhibit dopamine, norepinephrine, and serotonin transporters, with high dopamine transporter selectivity linked to abuse potential. In vitro testing of 58 substances showed that N-pyrrolidine cathinones combined with methylenedioxy groups—MDPiHP, MDPEP, and MDPV—had the highest potency at the dopamine transporter. Other N-pyrrolidine cathinones, such as 3F-α-PHP, 3F-α-PiHP, and 4F-α-PiHP, showed the greatest dopamine transporter selectivity relative to the serotonin transporter. Chloromethcathinone and methylmethcathinone compounds, like 3-CMC, displayed an amphetamine-like profile with comparable potency at dopamine and norepinephrine transporters. Some cathinones at high concentrations and phenethylamines at micromolar concentrations also activated the 5-HT2A receptor, while 2C-like arylcyclohexylamines targeted the receptor without transporter inhibition. The majority of compounds, especially N-pyrrolidine cathinones, suggest high abuse potential based on their dopamine transporter selectivity.