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Clinical data
Other namesSEP-363856; SEP-856
  • 1-[(7S)-5,7-dihydro-4H-thieno[2,3-c]pyran-7-yl]-N-methylmethanamine
CAS Number
PubChem CID
Chemical and physical data
Molar mass183.27 g·mol−1
3D model (JSmol)
  • CNC[C@H]1C2=C(CCO1)C=CS2
  • InChI=1S/C9H13NOS/c1-10-6-8-9-7(2-4-11-8)3-5-12-9/h3,5,8,10H,2,4,6H2,1H3/t8-/m0/s1

Ulotaront (INN;[1] 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.[2][3] The medication was discovered in collaboration between PsychoGenics Inc. and Sunovion Pharmaceuticals[2] using PsychoGenics' behavior and AI-based phenotypic drug discovery platform, SmartCube.[4] 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.[5] Treatment with ulotaront, as compared with placebo, was also associated with an improvement in sleep quality.[5] Ulotaront was awarded a Breakthrough Therapy designation due to its increased efficacy and greatly reduced side effects compared to current treatments.[6]

Adverse effects[edit]

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.[7] Some adverse events reported in preliminary clinical trials are somnolence, agitation, nausea, diarrhea, and dyspepsia.[7]


Mechanism of action[edit]

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.[2][8] This mechanism of action is unique among available antipsychotics, which generally antagonize dopamine receptors (especially dopamine D2 receptor).[9][10]


The precise pharmacokinetic profile of ulotaront has not been reported, though the developer has suggested that the pharmacokinetic data supports once daily dosing.[8]


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.[3][11][12] The U.S. Food and Drug Administration has granted ulotaront the breakthrough therapy designation.[8][13] In addition to schizophrenia, ulotaront is also being studied for the treatment of psychosis associated with Parkinson's disease.[13]

Interesting facts[edit]

Ulotaront and ralmitaront are TAAR1 agonists which have reached clinical trials.[14][15] The result of adding the first two letters of names "ralmitaront" and "ulotaront" to each other forms the name "Raul". Raul Gainetdinov is one of the pioneers in Trace-Amine Associated Receptors' research.[16][17]

See also[edit]


  1. ^ https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl124.pdf?sfvrsn=6437f035_10&download=true[bare URL PDF]
  2. ^ a b c "SEP 363856 - AdisInsight". adisinsight.springer.com. Adis International Ltd. Retrieved 29 December 2018.
  3. ^ a b Brooks M. "New Psychotropic Drug for Schizophrenia Promising in Early Testing". Medscape. Reuters Health Information. Retrieved 29 December 2018.
  4. ^ "Sunovion Presents Data From Marketed and Late-Stage Development Psychiatric Compounds At The American Psychiatric Association (APA) Annual Meeting 2021". www.businesswire.com. 2021-05-03. Retrieved 2021-09-09.
  5. ^ a b Koblan KS, Kent J, Hopkins SC, Krystal JH, Cheng H, Goldman R, Loebel A (April 2020). "A Non-D2-Receptor-Binding Drug for the Treatment of Schizophrenia". The New England Journal of Medicine. 382 (16): 1497–1506. doi:10.1056/NEJMoa1911772. PMID 32294346.
  6. ^ "Sunovion and PsychoGenics Announce that SEP-363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia". www.businesswire.com. 2019-05-10. Retrieved 2021-09-09.
  7. ^ a b Brooks M. "'Game Changer' for Schizophrenia on the Horizon?". Medscape. WebMD LLC. Retrieved 21 June 2019.
  8. ^ a b c "Sunovion and PsychoGenics Announce that SEP-363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia". Bloomberg.com. Bloomberg L.P. 10 May 2019. Retrieved 21 June 2019.
  9. ^ Koblan K, Hopkins S, Justine K, Hailong C, Goldman R, Loebel A (2019). "O12.5. Efficacy and Safety of Sep-363856, A Novel Psychotropic Agent with a Non-D2 Mechanism of Action, in the Treatment of Schizophrenia: A 4-Week, Randomized, Placebo-Controlled Trial". Schizophrenia Bulletin. 45 (Suppl 2): S199. doi:10.1093/schbul/sbz021.269. PMC 6455810.
  10. ^ Dedic N, Jones PG, Hopkins SC, Lew R, Shao L, Campbell JE, et al. (October 2019). "SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action". The Journal of Pharmacology and Experimental Therapeutics. 371 (1): 1–14. doi:10.1124/jpet.119.260281. PMID 31371483.
  11. ^ "Sunovion – Our Therapies". www.sunovion.us. Sumitomo Dainippon Pharma Co., Ltd. Retrieved 29 December 2018.
  12. ^ "About Us". www.psychogenics.com. PsychoGenics. Retrieved 29 December 2018.
  13. ^ a b "Drug Receives FDA's Breakthrough Therapy Designation for Treating Individuals with Schizophrenia". Pharmacy Times. Pharmacy & Healthcare Communications, LLC. Retrieved 21 June 2019.
  14. ^ "A Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adults With Schizophrenia". clinicaltrials.gov. 25 August 2021.{{cite journal}}: CS1 maint: url-status (link)
  15. ^ "A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder". clinicaltrials.gov. 22 September 2021.{{cite journal}}: CS1 maint: url-status (link)
  16. ^ Premont RT, Gainetdinov RR, Caron MG (2001-08-14). "Following the trace of elusive amines". Proceedings of the National Academy of Sciences. 98 (17): 9474–9475. Bibcode:2001PNAS...98.9474P. doi:10.1073/pnas.181356198. PMC 55475. PMID 11504935.
  17. ^ Gainetdinov RR, Hoener MC, Berry MD (July 2018). "Trace Amines and Their Receptors". Pharmacological Reviews. 70 (3): 549–620. doi:10.1124/pr.117.015305. PMID 29941461.

External links[edit]