Unraveling the In Vitro Toxicity Profile of Psychedelic 2C Phenethylamines and Their N-Benzylphenethylamine (NBOMe) Analogues
Pharmaceuticals August 15, 2023 Daniel Martins, Eva Gil-Martins, Fernando Cagide et al. 13 citations
Adding an N-2-methoxybenzyl group to mescaline and related 2C phenethylamine drugs to create NBOMe compounds significantly increases their in vitro toxicity to both brain (SH-SY5Y) and liver (HepG2) cell lines. The NBOMe drugs had lower EC50 values, indicating greater potency, and were able to cross the blood–brain barrier. The increased toxicity was linked to higher lipophilicity, disruption of mitochondrial membrane potential, and depletion of glutathione and ATP levels. Inhibition of cytochrome P450 enzymes, particularly CYP3A4 and CYP2D6, influenced the drugs' toxicity, suggesting these enzymes play a role in detoxification or bioactivation. No reactive oxygen species overproduction was detected.