ChemicalBook CAS DataBase List 1310422-41-3

1310422-41-3

Name	SEP-363856 HCl
CAS	1310422-41-3
Molecular Formula	C9H14ClNOS
MDL Number	MFCD32701938
Molecular Weight	219.73
MOL File	1310422-41-3.mol

Chemical Properties

solubility	DMSO:60.0(Max Conc. mg/mL);273.06(Max Conc. mM)
form	Solid
color	White to off-white

Safety Data

Symbol(GHS)	GHS07,GHS08
Signal word	Warning
Hazard statements	H373-H302-H319-H336
Precautionary statements	P264-P270-P301+P312-P330-P501-P261-P271-P304+P340-P312-P403+P233-P405-P501-P260-P314-P501-P264-P280-P305+P351+P338-P337+P313P

Hazard Information

Uses

SEP-363856 (SEP-856) hydrochloride, an orally active TAAR1 and 5-HT1A agonist and CNS active psychotropic agent with a unique, non-D2/5-HT2A mechanism of action, exerts its antipsychotic-like effects. SEP-363856 hydrochloride has the potential for the study of schizophrenia[1].

in vivo

SEP-856 (0.3, 1 and 10 mg/kg, i.p.) hydrochloride is CNS active and exhibits a behavioral signature similar to known antipsychotic drugs^[1].
SEP-856 (0.3, 1 and 10 mg/kg, orally once) hydrochloride significantly reduces PCP-induced hyperactivity^[1].
Oral SEP-856 hydrochloride 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^[1].

Animal Model:	Acute treatment with phencyclidine (PCP), which induces robust hyperactivity in rodents^[1].
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 (ED₅₀) of approximately 0.3 mg/kg.

Animal Model:	Male Sprague Dawley rats^[1].
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.

IC 50

TAAR1: 0.140 μM (EC₅₀); 5-HT_1A Receptor: 2.3 μM (EC₅₀); 5-HT_1B Receptor: 15.6 μM (EC₅₀); 5-HT_1D Receptor: 0.262 μM (EC₅₀); 5-HT_2A Receptor: >10 μM (EC₅₀); 5-HT_2C Receptor: 30 μM (EC₅₀); 5-HT₇ Receptor: 6.7 μM (EC₅₀)

References

[1] Dedic N, et al. SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action. J Pharmacol Exp Ther. 2019 Oct;371(1):1-14. DOI:10.1124/jpet.119.260281

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