RTI-7470-44

RTI-7470-44 is a highly potent and selective antagonist of the human trace amine-associated receptor 1 (hTAAR1), demonstrating an IC50 of 8.4 nM in an in vitro cAMP functional assay. In radioligand binding studies, it exhibits a Ki value of 0.3 nM, highlighting its strong affinity for hTAAR1. Notably, RTI-7470-44 shows significant species selectivity, with over 90-fold preference for hTAAR1 compared to its rat and mouse counterparts. This compound also possesses favorable pharmacokinetic properties, including good blood-brain barrier penetration, moderate metabolic stability, and a promising off-target safety profile. In electrophysiological studies, RTI-7470-44 enhanced the spontaneous firing rate of dopaminergic neurons in the mouse ventral tegmental area (VTA) and effectively counteracted the effects of the TAAR1 agonist RO5166017.