Ulotaront
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| Other names | SEP-363856; SEP-856 |
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| Formula | C9H13NOS |
| Molar mass | 183.27g·mol−1 |
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Ulotaront(INN;[1]developmental codesSEP-363856,SEP-856) is an investigationalantipsychoticthat is undergoingclinical trialsfor the treatment ofschizophreniaandParkinson's diseasepsychosis.[2][3]The medication was discovered in collaboration between PsychoGenics Inc. andSunovion Pharmaceuticals[2](which was subsequently merged into Sumitomo Pharma[4]) using PsychoGenics' behavior and AI-based phenotypic drug discovery platform, SmartCube.[5]Ulotaront is in Phase III of clinical development.
Research has shown that ulotaront results in a greater reduction from baseline in thePANSStotal score thanplacebo.[6]Treatment with ulotaront, as compared withplacebo,was also associated with an improvement insleepquality.[6]Ulotaront was awarded aBreakthrough Therapy designationdue to its increased efficacy and greatly reduced side effects compared to current treatments.[7]
Adverse effects
[edit]Theadverse effectprofile of ulotaront differs from that of other antipsychotics because itsmechanism of actiondoes not involveantagonismofdopamine receptorsin thebrain,which is responsible for the drug-inducedmovement disorders(likeakathisia) that may occur with those agents.[8]Some adverse events reported in preliminary clinical trials are somnolence, agitation, nausea, diarrhea, anddyspepsia.[8]
Pharmacology
[edit]Mechanism of action
[edit]The mechanism of action of ulotaront in the treatment of schizophrenia is unclear. However, it is thought to be anagonistat thetrace amine-associated receptor 1(TAAR1) andserotonin5-HT1Areceptors.[2][9]This mechanism of action is unique among available antipsychotics, which generally antagonize dopamine receptors (especiallydopamineD2receptor).[10][11]
Pharmacokinetics
[edit]The precisepharmacokineticprofile of ulotaront has not been reported, though the developer has suggested that the pharmacokinetic data supports once daily dosing.[9]
Research
[edit]As of 2018, Sunovion, the maker of another antipsychotic calledlurasidone(Latuda), is conducting clinical trials on ulotaront in partnership with the preclinical research company PsychoGenics.[3][12][13]The U.S.Food and Drug Administrationhas granted ulotaront thebreakthrough therapydesignation.[9][14]In addition to schizophrenia, ulotaront is also being studied for the treatment of psychosis associated withParkinson's disease.[14]
TheBrief Negative Symptom Scale(BNSS) has been used to assess the effect of Ulotaront on thenegative symptoms of schizophrenia.[15]
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.[16]
See also
[edit]References
[edit]- ^"International Nonproprietary Names for Pharmaceutical Substances (INN)"(PDF).WHO Drug Information.34(3). 2020.
Proposed INN: List 124 – COVID-19 (special edition)
- ^abc"SEP 363856".AdisInsight.Springer Nature Switzerland AG.Retrieved29 December2018.
- ^abBrooks M."New Psychotropic Drug for Schizophrenia Promising in Early Testing".Medscape.Reuters Health Information.Retrieved29 December2018.
- ^"US Sumitomo Pharma Subsidiaries Combine to Form Sumitomo Pharma America".American Pharmaceutical Review.7 April 2023.Retrieved10 July2023.
- ^"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.Retrieved2021-09-09.
- ^abKoblan 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.PMID32294346.
- ^"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.Retrieved2021-09-09.
- ^abBrooks M."'Game Changer' for Schizophrenia on the Horizon? ".Medscape.WebMD LLC.Retrieved21 June2019.
- ^abc"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.Retrieved21 June2019.
- ^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.PMC6455810.
- ^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-D2Receptor Mechanism of Action ".The Journal of Pharmacology and Experimental Therapeutics.371(1): 1–14.doi:10.1124/jpet.119.260281.PMID31371483.
- ^"Sunovion – Our Therapies".www.sunovion.us.Sumitomo Dainippon Pharma Co., Ltd.Retrieved29 December2018.
- ^"About Us".www.psychogenics.com.PsychoGenics.Retrieved29 December2018.
- ^ab"Drug Receives FDA's Breakthrough Therapy Designation for Treating Individuals with Schizophrenia".Pharmacy Times.Pharmacy & Healthcare Communications, LLC.Retrieved21 June2019.
- ^Tatsumi K, Kirkpatrick B, Strauss GP, Opler M (April 2020). "The brief negative symptom scale in translation: A review of psychometric properties and beyond".European Neuropsychopharmacology.33:36–44.doi:10.1016/j.euroneuro.2020.01.018.PMID32081498.S2CID211141678.
- ^Ernst D (2023-08-01)."Disappointing Results for Ulotaront in Two Phase 3 Schizophrenia Trials".Medical Professionals Reference.Retrieved2023-08-11.