Seltorexant

Seltorexant, also known by its developmental code names MIN-202 and JNJ-42847922, is an orexin antagonist medication which is under development for the treatment of depression and insomnia.[3][2] It is a selective antagonist of the orexin OX2 receptor (2-SORA).[2][4][1] The medication is taken by mouth.[1] As of February 2022, seltorexant is in phase 3 clinical trials for treatment of major depressive disorder (MDD) and phase 2 trials for treatment of insomnia.[3] It was also under investigation for the treatment of sleep apnea, but no recent development has been reported for this indication.[3] Seltorexant is under development by Minerva Neurosciences and Johnson & Johnson's Janssen Pharmaceuticals.[3]

Seltorexant
Clinical data
Other namesMIN-202; JNJ-42847922; JNJ-922
Routes of
administration		By mouth[1]
Drug classOrexin antagonist
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
MetabolismCYP3A4[2]
Elimination half-life2–3 hours[2]
Identifiers
IUPAC name
  • [5-(4,6-Dimethylpyrimidin-2-yl)-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-ylphenyl)methanone
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC21H22FN7O
Molar mass407.453 g·mol−1
3D model (JSmol)
SMILES
  • c4c(C)nc(nc4C)N5CC2CN(CC2C5)C(=O)c1c(cccc1F)-n3nccn3
InChI
  • InChI=1S/C21H22FN7O/c1-13-8-14(2)26-21(25-13)28-11-15-9-27(10-16(15)12-28)20(30)19-17(22)4-3-5-18(19)29-23-6-7-24-29/h3-8,15-16H,9-12H2,1-2H3/t15-,16+
  • Key:SQOCEMCKYDVLMM-IYBDPMFKSA-N

Seltorexant is being explored at doses of 5 to 80 mg.[2] In the early clinical trials conducted so far, seltorexant has been found to improve depression scores on the Hamilton Depression Rating Scale in people with MDD and to improve sleep onset, total sleep time, time awake after sleep onset, and sleep efficiency in people with MDD and/or insomnia.[2][4] Seltorexant is reported to be safe and well-tolerated.[2][4] Side effects of seltorexant observed in clinical trials so far have included somnolence, fatigue, dizziness, headache, abdominal discomfort, and nightmares.[2]

Seltorexant shows over 100-fold greater binding affinity for the OX2 receptor over the OX1 receptor.[4] This is in contrast to other orexin receptor antagonists like suvorexant, lemborexant, and daridorexant, which are all dual orexin receptor antagonists (DORAs).[4][2] Seltorexant has fast absorption with a time to peak levels of 0.3 to 1.5 hours and has a relatively short duration with an elimination half-life of only 2 to 3 hours.[2][4] No residual effects of the medication were observed 4 hours after daytime administration.[2] The pharmacokinetics of seltorexant are considered to be ideal for sleep induction.[4] Seltorexant is metabolized by the cytochrome P450 enzyme CYP3A4.[2] It is a small-molecule compound and is structurally related to other clinically used orexin receptor antagonists.[5][2]

See also

References
  1. Sun Y, Tisdale RK, Kilduff TS (2021). "Hypocretin/Orexin Receptor Pharmacology and Sleep Phases". Front Neurol Neurosci. 45: 22–37. doi:10.1159/000514963. PMID 34052813.
  2. Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J (November 2020). "Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders". Expert Opin Drug Metab Toxicol. 16 (11): 1063–1078. doi:10.1080/17425255.2020.1817380. PMID 32901578. S2CID 221572078.
  3. "Seltorexant - Janssen Research & Development/Minerva Neurosciences". AdisInsight. 2022-02-28. Retrieved 2022-04-05.
  4. Jacobson LH, Hoyer D, de Lecea L (January 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". J Intern Med. doi:10.1111/joim.13406. PMID 35043499.
  5. Christopher JA (2014). "Small-molecule antagonists of the orexin receptors". Pharmaceutical Patent Analyst. 3 (6): 625–38. doi:10.4155/ppa.14.46. PMID 25489915.
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