SEP-363856 (hydrochloride)

SEP-363856 is an agonist of trace amine-associated receptor 1 (TAAR1).¹ It increases intracellular cAMP levels in cells expressing TAAR1 (EC₅₀ = 0.14 µM). It is also an agonist of the serotonin (5-HT) receptor subtypes 5-HT_1D and 5-HT_1A, decreasing cAMP levels in cells expressing these receptors (EC₅₀s = 0.262 and 2.3 µM, respectively). SEP-363856 is selective for these receptors over the dopamine D_2L receptor (EC₅₀s = 10.44 and 8.02 µM in cAMP and arrestin recruitment assays, respectively), as well as α_2A- and α_2B-adrenergic, and 5-HT_1B, 5-HT_2A, 5-HT_2C, and 5-HT₇ receptors (EC₅₀s = 6.7->10 µM in functional assays). It reduces hyperactivity induced by phencyclidine (PCP) in mice when administered at 0.3, 1, and 3 mg/kg and reverses PCP-induced impairments in social interaction in rats. SEP-363856 (3, 10, and 30 mg/kg) increases prepulse inhibition of the acoustic startle response in mice. It also decreases the time spent immobile in the forced swim test in mice, indicating antidepressant-like activity.

WARNING This product is not for human or veterinary use.

1. Dedic, N., Jones, P.G., Hopkins, S.C., et al. SEP-363856, a novel psychotropic agent with a unique, non-D₂ receptor mechanism of action. J. Pharmacol. Exp. Ther. 371(1), 1-14 (2019).