Ulotaront

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Ulotaront (SEP-363856) is an investigational antipsychotic being studied for schizophrenia and Parkinson’s disease psychosis. It was discovered by PsychoGenics in collaboration with Sunovion (now Sumitomo Pharma) using AI-based drug discovery.

How it works
- Ulotaront activates the TAAR1 receptor and partially activates serotonin 5-HT1A receptors. Unlike many antipsychotics, it does not block dopamine D2 receptors, which may lead to fewer movement-related side effects.

Clinical status and goals
- It has received Breakthrough Therapy designation from the FDA because of its potential to provide strong benefits with a different side-effect profile.
- It is in phase III trials for schizophrenia and in phase II/III trials for generalized anxiety disorder and major depressive disorder. Trials for narcolepsy and some other psychotic disorders have been discontinued.

Efficacy and safety
- Some studies showed greater improvement than placebo on the PANSS scale (a measure of schizophrenia symptoms) and better sleep.
- In July 2023, a study in acutely psychotic schizophrenia patients did not show a clear advantage over placebo on the primary PANSS outcome.
- Common side effects reported in early trials include sleepiness, agitation, nausea, diarrhea, and upset stomach. Because it works differently from typical antipsychotics, it may have a lower risk of movement disorders.

Bottom line
- Ulotaront is still being studied and is not approved yet. It represents a new approach to antipsychotic treatment, focusing on TAAR1 and 5-HT1A receptors rather than direct dopamine receptor blockade.