Ulotaront hydrochloride (SEP-363856, SEP-856) is a psychotropic agent and selective agonist of trace amine receptor 1 (TAAR1) and 5-HT1A receptor with EC50 of 0.14 uM and 2.3 uM for human TAAR1 and 5-HT1A receptor respectively, shows no appreciable action at dopamine D2 receptors.
Ulotaront (SEP-363856, SEP-856) exhibits weak partial agonism with EC50 values of 10.44 ± 4 µM (cAMP, Emax = 23.9% ± 7.6%; Fig. 2C) and 8 µM (β-arrestin recruitment, Emax = 27.1%) in D2 receptor functional assays.
Ulotaront (SEP-363856, SEP-856) demonstrates antipsychotic- and antidepressant-like activity without inducing catalepsy.
Ulotaront (SEP-363856, SEP-856) decreases REM sleep in rats.
Ulotaront (SEP-363856, SEP-856) does not exhibit significant occupancy at D2 receptors in nonhuman primates.
Ulotaront (SEP-363856, SEP-856) induces significant inhibitory responses in DPAT-sensitive neurons of the DRN and a subset of VTA neurons.
Ulotaront (SEP-363856, SEP-856) inhibits firing of DRN in vivo and partially attenuates PCP-induced hyperactivity through 5-HT1A receptors.
Ulotaront (SEP-363856, SEP-856) demonstrated broad efficacy in putative rodent models relating to aspects of schizophrenia, including phencyclidine (PCP)-induced hyperactivity, prepulse inhibition, and PCP-induced deficits in social interaction.