SEP-363856 hydrochloride (SEP-856 hydrochloride), an orally active and CNS active psychotropic agent with a unique, non-D2/5-HT2A mechanism of action, exerts its antipsychotic-like effects. SEP-363856 hydrochloride (SEP-856 hydrochloride) has the potential for the study of schizophrenia
In Vitro
SEP-856 (10 μM) shows >50% inhibition of specific binding at α 2A , α 2B , D 2 , 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 2A , 5-HT 2B , 5-HT 2C , and 5-HT 7 receptors. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
SEP-856 (0.3, 1 and 10 mg/kg, i.p.) is CNS active and exhibits a behavioral signature similar to known antipsychotic drugs . SEP-856 (0.3, 1 and 10 mg/kg, orally once) significantly reduces PCP-induced hyperactivity . Oral SEP-856 administration (1, 3 and 10 mg/kg) produces a dosedependent decrease in REM sleep, increase in latency to REM sleep and increase in cumulative wake (W) time . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Acute treatment with phencyclidine (PCP), which induces robust hyperactivity in rodents . Dosage: 0.3, 1 and 3 mg/kg. Administration: Orally once. Result: Resulted in a dose-dependent inhibition of PCP-induced hyperactivity responses in C57Bl/6J mice (1-way ANOVA F (5, 59) = 18.96, p < 0.0001; Tukey’s post-hoc test, p < 0.05) with a 50% effective dose (ED 50 ) of approximately 0.3 mg/kg. Animal Model: Male Sprague Dawley rats . Dosage: 1, 2, and 5 mg/kg. Administration: I.V. injection. (Pharmacokinetic Analysis). Result: Rapidly absorbed with maximum plasma and brain concentrations reached within 0.25 to 0.5 hours in mice and rats and maximum plasma concentrations reached within 6 ± 2.83 hours in monkeys. Penetrated mouse and rat brains after oral administration (10 mg/kg), with average brain-to-plasma AUC ratios of ~3 respectively.
Form:Solid
IC50& Target:TAAR1 0.140 μM (EC 50 ) 5-HT 1A Receptor 2.3 μM (EC 50 ) 5-HT 1B Receptor 15.6 μM (EC 50 ) 5-HT 1D Receptor 0.262 μM (EC 50 ) 5-HT 2A Receptor >10 μM (EC 50 ) 5-HT 2C Receptor 30 μM (EC 50 ) 5-HT 7 Receptor 6.7 μM (EC 50 )
