Vornorexant (ORN-0829; TS-142) is a potent dual OX1R and OX2R antagonist with IC50 values of 1.05 nM and 1.27 nM, respectively. It exhibits potent sleep-promoting effects in vivo and can be used for insomnia treatment research.

Vornorexant, when administered orally to rats at dosages ranging from 1 to 10 mg/kg, demonstrates significant sleep-inducing and sleep-promoting effects, as evidenced by a dose-dependent increase in total sleep percentage observed in a rat polysomnogram study at a 1 mg/kg dose. Additionally, Vornorexant displays favorable pharmacokinetic characteristics, characterized by a swift maximum concentration (T max) and brief elimination half-lives in both rats and dogs, with half-lives of 0.238 hours in rats and 1.16 hours in dogs. Administered to rats before the onset of their active phase (prior to lights off), the compound has shown promising efficacy in sleep enhancement at dosages of 1, 3, and 10 mg/kg.