Archives of Toxicology
July 5, 2020
Eline Pottie, Annelies Cannaert, Christophe P. Stove
36 citations
Serotonergic psychedelics, which act mainly through the serotonin 2A receptor, make up many new psychoactive substances. A stable cell-based bioassay using HEK 293 T cells was developed to monitor β-arrestin 2 recruitment to the 5-HT2AR. After verifying its performance against a transient transfection system, the assay was used to test 30 phenylalkylamine psychedelics: 12 phenethylamine derivatives (2C-X), 7 phenylisopropylamines (DOx), and 11 N-benzylderivatives (25X-NB). The resulting potency and efficacy values confirm findings from other in vitro assays and show a significant correlation with estimated common doses. This approach offers pharmacological insights and may help prioritize legal actions regarding the most potent compounds.
Analytical Chemistry
November 14, 2019
Eline Pottie, Annelies Cannaert, Katleen van Uytfanghe et al.
29 citations
Classic hallucinogens, which activate the serotonin 2A receptor (5-HT2AR), represent the third largest category of new psychoactive substances. A new bioassay was developed that measures receptor activation by monitoring β-arrestin2 recruitment using a split-luciferase system. The assay determined potency and efficacy for various hallucinogens, including LSD, 5-MeO-DALT, mescaline, and several 2C compounds and their NBOMe derivatives, with EC50 values ranging from subnanomolar (NBOMes) to micromolar (mescaline) levels. When applied to plasma screening, blank samples showed pronounced receptor activation due to endogenous serotonin, confirmed by its elimination with a 5-HT2AR antagonist or MAO-A treatment, and by LC-HRMS analysis. The bioassay's main application is characterizing poorly understood serotonergic hallucinogens, as MAO-A metabolism of some compounds could bias detection in biofluids.
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.
Archives of toxicology
October 1, 2020
Eline Pottie, Annelies Cannaert, Christophe P Stove
correction
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