Ulotaront

Ulotaront (INN; developmental codes SEP-363856, SEP-856) is an investigational antipsychotic that is undergoing clinical trials for the treatment of schizophrenia and Parkinson's disease psychosis. The medication was discovered in collaboration between PsychoGenics Inc. and Sunovion Pharmaceuticals (which was subsequently merged into Sumitomo Pharma ) using PsychoGenics' behavior and AI-based phenotypic drug discovery platform, SmartCube. Ulotaront is in Phase III of clinical development.

Research has shown that ulotaront results in a greater reduction from baseline in the PANSS total score than placebo. Treatment with ulotaront, as compared with placebo, was also associated with an improvement in sleep quality. Ulotaront was awarded a Breakthrough Therapy designation due to its increased efficacy and greatly reduced side effects compared to current treatments.

Adverse effects
The adverse effect profile of ulotaront differs from that of other antipsychotics because its mechanism of action does not involve antagonism of dopamine receptors in the brain, which is responsible for the drug-induced movement disorders (like akathisia) that may occur with those agents. Some adverse events reported in preliminary clinical trials are somnolence, agitation, nausea, diarrhea, and dyspepsia.

Mechanism of action
The mechanism of action of ulotaront in the treatment of schizophrenia is unclear. However, it is thought to be an agonist at the trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors. This mechanism of action is unique among available antipsychotics, which generally antagonize dopamine receptors (especially dopamine D2 receptor).

Pharmacokinetics
The precise pharmacokinetic profile of ulotaront has not been reported, though the developer has suggested that the pharmacokinetic data supports once daily dosing.

Research
As of 2018, Sunovion, the maker of another antipsychotic called lurasidone (Latuda), is conducting clinical trials on ulotaront in partnership with the preclinical research company PsychoGenics. The U.S. Food and Drug Administration has granted ulotaront the breakthrough therapy designation. In addition to schizophrenia, ulotaront is also being studied for the treatment of psychosis associated with Parkinson's disease.

The Brief Negative Symptom Scale (BNSS) has been used to assess the effect of Ulotaront on the negative symptoms of schizophrenia.

In July 2023, the pharmaceutical company behind the drug announced that the drug had failed to outperform placebo in the treatment of acutely psychotic patients with schizophrenia, as measured by the PANSS.