Ulotaront

What it is

Ulotaront acts on TAAR1, a receptor that regulates how much dopamine nerve cells release, and on the serotonin 5-HT1A receptor. It does not block dopamine receptors.^1,2

How it works

In a brain-scan study, 22 people with schizophrenia took ulotaront or a placebo for two weeks alongside their antipsychotic. Ulotaront reduced how much dopamine the striatum produces, and those in whom it fell more had a larger fall in hallucinations and delusions.³ It therefore acts on the step that brain scans have found raised in schizophrenia, the production of dopamine, rather than on its receptor, as explained in Beyond dopamine (opens in a new tab).

How well it works

In a four-week phase 2 trial of 245 people, symptoms fell by 17.2 points on ulotaront and 9.7 on placebo.²

Two six-week phase 3 trials, with 435 and 464 people, did not confirm it: no dose did better than placebo. The makers attributed this partly to an unusually large improvement on placebo, possibly linked to the COVID-19 pandemic.¹ A new phase 3 trial with 538 people has finished enrolling, and its results are expected after October 2026.⁴ A related medicine from Roche, ralmitaront, did not beat placebo, and its trial in negative symptoms was stopped early.^5,6

Side effects

In the phase 2 trial, sleepiness and digestive complaints were the most common side effects, and one person taking ulotaront died suddenly of a heart problem.² Across trials, anxiety was about twice as common on the 75 mg dose as on placebo.⁷

What we don’t know yet

• Whether the new phase 3 trial confirms a benefit.
• Whether acting on dopamine production, rather than on its receptor, helps people whom antipsychotics have not helped.