Ulotaront

Last updated
Ulotaront
SEP-363856.svg
Clinical data
Other namesSEP-363856; SEP-856
Identifiers
  • 1-[(7S)-5,7-dihydro-4H-thieno[2,3-c]pyran-7-yl]-N-methylmethanamine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
Chemical and physical data
Formula C9H13NOS
Molar mass 183.27 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
  • Key:ABDDQTDRAHXHOC-QMMMGPOBSA-N

Ulotaront (INN Tooltip International Nonproprietary Name; [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] (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.

Contents

Research has shown that ulotaront results in a greater reduction from baseline in the PANSS total score than placebo. [6] Treatment with ulotaront, as compared with placebo, was also associated with an improvement in sleep quality. [6] Ulotaront was awarded a Breakthrough Therapy designation due to its increased efficacy and greatly reduced side effects compared to current treatments. [7]

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. [8] Some adverse events reported in preliminary clinical trials are somnolence, agitation, nausea, diarrhea, and dyspepsia. [8]

Pharmacology

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. [2] [9] This mechanism of action is unique among available antipsychotics, which generally antagonize dopamine receptors (especially dopamine D2 receptor). [10] [11]

Pharmacokinetics

The precise pharmacokinetic profile of ulotaront has not been reported, though the developer has suggested that the pharmacokinetic data supports once daily dosing. [9]

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. [3] [12] [13] The U.S. Food and Drug Administration has granted ulotaront the breakthrough therapy designation. [9] [14] In addition to schizophrenia, ulotaront is also being studied for the treatment of psychosis associated with Parkinson's disease. [14]

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

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

<span class="mw-page-title-main">Chlorpromazine</span> Antipsychotic medication

Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Risperidone</span> Antipsychotic medication

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. It is taken orally.

<span class="mw-page-title-main">Ziprasidone</span> Antipsychotic medication

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia, obsessive compulsive disorder (OCD), and bipolar disorder; other uses include as an add-on treatment in major depressive disorder, tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Armodafinil</span> Eugeroic medication

Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (R)-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. and was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Iloperidone</span> Atypical antipsychotic medication

Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.

<span class="mw-page-title-main">Perospirone</span> Atypical antipsychotic medication

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

<span class="mw-page-title-main">Lurasidone</span> Atypical antipsychotic medication

Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">Pimavanserin</span> Atypical antipsychotic medication

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer's disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.

<span class="mw-page-title-main">Dasotraline</span> Chemical compound

Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that was under development by Sunovion for the treatment of attention-deficit hyperactivity disorder (ADHD) and binge eating disorder (BED). Structurally, dasotraline is a stereoisomer of desmethylsertraline (DMS), which is an active metabolite of the marketed selective serotonin reuptake inhibitor (SSRI) antidepressant sertraline (Zoloft).

<span class="mw-page-title-main">Pomaglumetad</span> Drug, used as a treatment for schizophrenia

Pomaglumetad (LY-404,039) is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pharmacological research has focused on its potential antipsychotic and anxiolytic effects. Pomaglumetad is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. Human studies investigating therapeutic use of pomaglumetad have focused on the prodrug LY-2140023, a methionine amide of pomaglumetad (also called pomaglumetad methionil) since pomaglumetad exhibits low oral absorption and bioavailability in humans.

<span class="mw-page-title-main">Cariprazine</span> Atypical antipsychotic medicine

Cariprazine, sold under the brand names Vraylar,Reagila and Symvenu among others, is an atypical antipsychotic originated by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, bipolar depression, and major depressive disorder. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. It is taken by mouth.

<span class="mw-page-title-main">Brexpiprazole</span> Atypical antipsychotic

Brexpiprazole, sold under the brand name Rexulti among others, is a medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease. It is an atypical antipsychotic.

<span class="mw-page-title-main">Brilaroxazine</span> Experimental atypical antipsycotic

Brilaroxazine, also known as oxaripiprazole, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment of neuropsychiatric and inflammatory disorders. It has currently completed the first of two phase III clinical trials for schizophrenia. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, attention deficit hyperactivity disorder (ADD/ADHD), psychosis/agitation associated with Alzheimer's disease, Parkinson's disease psychosis, as well as the inflammatory disorders pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and psoriasis. The FDA granted brilaroxazine orphan drug designation for the treatment of PAH and IPF.

References

  1. "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 34 (3). 2020. Proposed INN: List 124 – COVID-19 (special edition)
  2. 1 2 3 "SEP 363856". AdisInsight. Springer Nature Switzerland AG. Retrieved 29 December 2018.
  3. 1 2 Brooks M. "New Psychotropic Drug for Schizophrenia Promising in Early Testing". Medscape. Reuters Health Information. Retrieved 29 December 2018.
  4. "US Sumitomo Pharma Subsidiaries Combine to Form Sumitomo Pharma America". American Pharmaceutical Review. 7 April 2023. Retrieved 10 July 2023.
  5. "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.
  6. 1 2 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.
  7. "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.
  8. 1 2 Brooks M. "'Game Changer' for Schizophrenia on the Horizon?". Medscape. WebMD LLC. Retrieved 21 June 2019.
  9. 1 2 3 "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.
  10. 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 .
  11. 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.
  12. "Sunovion – Our Therapies". www.sunovion.us. Sumitomo Dainippon Pharma Co., Ltd. Retrieved 29 December 2018.
  13. "About Us". www.psychogenics.com. PsychoGenics. Retrieved 29 December 2018.
  14. 1 2 "Drug Receives FDA's Breakthrough Therapy Designation for Treating Individuals with Schizophrenia". Pharmacy Times. Pharmacy & Healthcare Communications, LLC. Retrieved 21 June 2019.
  15. 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. PMID   32081498. S2CID   211141678.
  16. Ernst D (2023-08-01). "Disappointing Results for Ulotaront in Two Phase 3 Schizophrenia Trials". Medical Professionals Reference. Retrieved 2023-08-11.