Seltorexant,also known by its developmental code namesMIN-202andJNJ-42847922,is anorexin antagonistmedicationwhich is under development for the treatment ofdepressionandinsomnia.[3][2]It is aselectiveantagonistof theorexinOX2receptor(2-SORA).[2][4][1]The medication is takenby mouth.[1]
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| Other names | MIN-202; JNJ-42847922; JNJ-922 |
| Routes of administration | By mouth[1] |
| Drug class | Orexin antagonist |
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| Pharmacokineticdata | |
| Metabolism | CYP3A4[2] |
| Eliminationhalf-life | 2–3 hours[2] |
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| Formula | C21H22FN7O |
| Molar mass | 407.453g·mol−1 |
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Pharmacology
editPharmacokinetics
editSeltorexant has fastabsorptionwith atime to peaklevels of 0.3 to 1.5hours and has a relatively shortdurationwith anelimination half-lifeof only 2 to 3hours.[2][4]No residual effects of the medication were observed 4hours after daytime administration.[2]Thepharmacokineticsof seltorexant are considered to be ideal forsleep induction.[4]Seltorexant ismetabolizedby thecytochrome P450enzymeCYP3A4.[2]
Mechanism of action
editIt is asmall-moleculecompound and isstructurallyrelated to other clinically used orexin receptor antagonists.[5][2]Seltorexant shows over 100-fold greaterbinding affinityfor the OX2receptor over theOX1receptor.[4]This is in contrast to other orexin receptor antagonists likesuvorexant,lemborexant,anddaridorexant,which are alldual orexin receptor antagonists(DORAs).[4][2]
Clinical trials
editAs of February 2022, seltorexant is inphase 3clinical trialsfor treatment ofmajor depressive disorder(MDD) andphase 2trials for treatment of insomnia.[3]It was also under investigation for the treatment ofsleep apnea,but no recent development has been reported for this indication.[3]Seltorexant is under development by Minerva Neurosciences andJohnson & Johnson'sJanssen Pharmaceuticals.[3]
Seltorexant is being explored at doses of 5 to 80mg.[2]In the early clinical trials conducted so far, seltorexant has been found to improve depression scores on theHamilton Depression Rating Scalein people with MDD and to improvesleep onset,total sleep time,time awake after sleep onset,andsleep efficiencyin people with MDD and/or insomnia.[2][4]Seltorexant is reported to besafeandwell-tolerated.[2][4]Side effectsof seltorexant observed in clinical trials so far have includedsomnolence,fatigue,dizziness,headache,abdominal discomfort,andnightmares.[2]
See also
edit- Vornorexant– another investigational short-acting orexin receptor antagonist
- List of investigational antidepressants § Orexin receptor antagonists
- List of investigational sleep drugs § Orexin receptor antagonists
References
edit- ^abcSun Y, Tisdale RK, Kilduff TS (2021)."Hypocretin/Orexin Receptor Pharmacology and Sleep Phases".Front Neurol Neurosci.Frontiers of Neurology and Neuroscience.45:22–37.doi:10.1159/000514963.ISBN978-3-318-06843-6.PMC8171809.PMID34052813.
- ^abcdefghijklmMuehlan 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.PMID32901578.S2CID221572078.
- ^abcd"Seltorexant - Janssen Research & Development/Minerva Neurosciences".AdisInsight. 2022-02-28.Retrieved2022-04-05.
- ^abcdefgJacobson LH, Hoyer D, de Lecea L (January 2022). "Hypocretins (orexins): The ultimate translational neuropeptides".J Intern Med.291(5): 533–556.doi:10.1111/joim.13406.PMID35043499.S2CID248119793.
- ^Christopher JA (2014). "Small-molecule antagonists of the orexin receptors".Pharmaceutical Patent Analyst.3(6): 625–38.doi:10.4155/ppa.14.46.PMID25489915.