Ultrapotent PSEM (uPSEM) agonist for PSAM4-GlyR and PSAM4-5HT3 (Ki = 0.7 nM for PSAM4-GlyR and <10 nM for PSAM4-5HT3). Exhibits >10,000-fold agonist selectivity for PSAM4-GlyR over α7-GlyR, α7-5HT3, and 5HT3-R, and 230-fold selectivity over α4β2 nAChR. Also weak partial agonist (~10 %) at α4β2 nAChR. Retains the potency of varenicline (Cat.No. 3754) for PSAM4-GlyR with enhanced chemogenetic selectivity. Does not act as a substrate for P-glycoprotein pumps. Silences neurons in vivo. Brain-penetrant.
Magnus et al (2019) Ultrapotent chemogenetics for research and potential clinical applications. Science doi: 10.1126/science PMID:30872534