Identification of psychedelic new psychoactive substances (NPS) showing biased agonism at the 5-HT2AR through simultaneous use of β-arrestin 2 and miniGαq bioassays.
Biochemical Pharmacology September 27, 2020 E. Pottie, P. Dedecker, C. Stove
Psychedelic new psychoactive substances (NPS) that activate the serotonin 2A receptor (5-HT2AR) remain a large share of reported NPS, but their exact mechanisms—especially what distinguishes them from non-psychedelic 5-HT2AR agonists—need more study. A new bioassay was developed to monitor recruitment of an engineered miniGαq protein to the activated 5-HT2AR, designed to parallel an existing assay for β-arrestin 2 recruitment. This allowed estimation of a substance's preference for triggering one protein over the other (biased agonism).