Vornorexant Explained

Vornorexant, also known by its developmental code names ORN-0829 and TS-142, is an orexin antagonist medication which is under development for the treatment of insomnia and sleep apnea.^{[1] [2] [3]} It is a dual orexin OX₁ and OX₂ receptor antagonist (DORA).^[4] The medication is taken by mouth.^[5] As of June 2021, vornorexant is in phase 2 clinical trials for insomnia and phase 1 trials for sleep apnea. It is under development by Taisho Pharmaceutical.

Vornorexant has a time to peak of 2.5hours and a relatively short elimination half-life of 1.3 to 3.3hours.^[6] It was designed to have a short half-life and duration in order to reduce next-day side effects like somnolence.

See also

• Seltorexant – another investigational short-acting orexin receptor antagonist
• List of investigational sleep drugs § Orexin receptor antagonists

External links

• Vornorexant (ORN-0829, TS-142) - AdisInsight

Notes and References

1. Web site: TS 142 - AdisInsight.
2. Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J . Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders . Expert Opinion on Drug Metabolism & Toxicology . 16 . 11 . 1063–1078 . November 2020 . 32901578 . 10.1080/17425255.2020.1817380 . 221572078 .
3. Jacobson LH, Hoyer D, de Lecea L . Hypocretins (orexins): The ultimate translational neuropeptides . Journal of Internal Medicine . 291 . 5 . 533–556 . May 2022 . 35043499 . 10.1111/joim.13406 . 248119793 .
4. Futamura A, Suzuki R, Tamura Y, Kawamoto H, Ohmichi M, Hino N, Tokumaru Y, Kirinuki S, Hiyoshi T, Aoki T, Kambe D, Nozawa D . 6 . Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia . Bioorganic & Medicinal Chemistry . 28 . 13 . 115489 . July 2020 . 32482533 . 10.1016/j.bmc.2020.115489 . 216517776 .
5. Uchiyama M, Kambe D, Imadera Y, Kajiyama Y, Ogo H, Uchimura N . Effects of TS-142, a novel dual orexin receptor antagonist, on sleep in patients with insomnia: a randomized, double-blind, placebo-controlled phase 2 study . Psychopharmacology . 239 . 7 . 2143–2154 . July 2022 . 35296912 . 10.1007/s00213-022-06089-6 . free . 9205809 .
6. Uchiyama M, Kambe D, Imadera Y, Sunaga H, Hasegawa S, Nogi T, Kajiyama Y, Yoshida S, Ogo H, Uchimura N . 0146 Efficacy and Safety of Single Dose of TS-142, a Novel and Potent Dual Orexin Receptor Antagonist, in Insomnia Patients . Sleep . April 2020 . 43 . Supplement 1 . A58 . 0161-8105 . 1550-9109 . 10.1093/sleep/zsaa056.144 . free .