Forced swimming test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model
Oral
0.1, 0.3, 1, 3, 10, 15 mg/kg
Single administration or 21-day continuous administration
To evaluate the antidepressant-like effects of SEP-363856 alone or in combination with duloxetine. Results showed that SEP-856 exhibited antidepressant-like effects in FST and TST, especially at doses of 0.3, 1, and 10 mg/kg. Compared with duloxetine alone, the combination of duloxetine and SEP-856 produced more significant antidepressant-like effects in FST and TST. In the CUMS model, both SEP-856 and duloxetine alone or in combination reversed the CUMS-induced reduction in sucrose preference.
Molecules. 2022 Apr 25;27(9):2755
Rats
Healthy rats
Oral
1, 3 or 10 mg/kg
Single dose
Evaluate the ability of SEP-856 to modulate the activity of specific brain regions under basal conditions
Int J Mol Sci. 2021 Apr 16;22(8):4119
ICR mice
Schizophrenia models
Oral
1, 3, 10 mg/kg
Single administration
To evaluate the antipsychotic effects of SEP-363856 in combination with olanzapine in the apomorphine (APO)-induced climbing test
Molecules. 2022 Apr 14;27(8):2550
Mice
Drd1a-tdTomato mice and C57BL/6J mice
Bath application
10 μM and 30 μM
15 minutes
To evaluate the effect of ulotaront on spontaneous neuronal firing and excitatory synaptic transmission in hippocampal CA1, results showed that ulotaront reduced spontaneous neuronal firing and enhanced excitatory synaptic transmission.
Neuropsychopharmacology. 2024 Jun;49(7):1091-1103
Human
Patients with schizophrenia
Oral
25/50/75 mg/d
Once daily for 26 weeks
To evaluate the long-term safety and effectiveness of ulotaront in patients with schizophrenia. Results showed minimal changes in body weight, cholesterol, triglycerides, and prolactin, with no extrapyramidal effects. Significant improvements were observed in PANSS total score and CGI-S score.
NPJ Schizophr. 2021 Dec 9;7(1):63
Mice
C57BL/6 wild-type mice
Intraperitoneal injection
3 mg/kg
Single administration
To test the effect of SEP-363856 on reversing the ketamine-induced increase in striatal dopamine synthesis capacity. Results showed that SEP-363856 significantly reduced the ketamine-induced increase in dopamine synthesis capacity.
Mol Psychiatry. 2021 Jun;26(6):2562-2576
Humans
Patients with schizophrenia and healthy volunteers
Oral
5–150 mg/day
Once daily for 7 days
To evaluate the population pharmacokinetics (PopPKs) of ulotaront in adult subjects and characterize potential pharmacokinetic covariates. Results showed that ulotaront exhibited dose-proportionality in doses ranging from 10 to 100 mg, was well-absorbed, and had moderate interindividual variability.
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