Pharmacodynamics<unk>  acts as a selective dual antagonist of the orexin (hypocretin) receptors OX1 and OX2. The affinities (Ki) of<unk>  for the orexin receptors are 0.47nM for the OX1 receptor and 0.93nM for the OX2 receptor. Its Kb values for the human orexin receptors have been reported to be 0.5nM for the OX1 receptor and 0.8nM for the OX2 receptor. Hence,<unk>  is approximately equipotent in its antagonism of the orexin receptors.<unk>  is selective for the orexin receptors over many other targets. In contrast to certain other sedatives and hypnotics,<unk>  is not a benzodiazepine or Z-drug and does not interact with GABA receptors. Mechanism of action The endogenous orexin neuropeptides, orexin A and orexin B, are involved in the regulation of sleep–wake cycles and act to promote wakefulness. Deficiency of orexin signaling is thought to be the primary cause of the sleep disorder narcolepsy. Disturbances in orexin signaling may also be involved in insomnia. Research suggests that orexin signaling may change with age, and this has been implicated in age-related sleep disturbances. By blocking the actions of orexins and modulating sleep–wake cycles, orexin receptor antagonists like<unk>  reduce wakefulness and improve sleep. The sleep-promoting effects of dual orexin receptor antagonists are thought to be mediated specifically by blockade of the OX2 receptor in the lateral hypothalamus. Although narcoleptic symptoms were a theoretical concern during the development of orexin receptor antagonists, this has not been observed in clinical trials of these agents. Pharmacokinetics<unk>  levels after a single oral dose of 50 to 150mg<unk>  in healthy recreational sedative drug users. Absorption The absolute bioavailability of<unk>  is 62%. It reaches peak concentrations within 1 to 2hours following a dose. Food prolonged the time to peak by 1.3hours and decreased the peak concentrations by 16%, but did not affect area-under-the-curve concentrations. Distribution The volume of distribution of<unk>  is 31L. Its plasma protein binding is 99.7%. The plasma-to-blood ratio of<unk>  is 0.64.<unk>  effectively crosses the blood–brain barrier in animals. Metabolism<unk>  is extensively metabolized primarily by CYP3A4 (89%). Other cytochrome P450 enzymes contribute individually to less than 3% of the clearance of<unk> . Elimination<unk>  is eliminated primarily by feces (57%) then by urine (28%). It is excreted mainly in the form of metabolites, with only trace amounts of the parent compound identified. The medication has an elimination half-life of about 8hours or of 6 to 10hours. Its half-life is shorter than that of other orexin receptor antagonists such as suvorexant (12hours) and lemborexant (~18–55hours). The relatively short half-life of<unk>  may allow for reduced daytime sedation. The duration of action of<unk>  in terms of sedative effects is approximately 8hours with a 50mg dose.
Daridorexant
Seltorexant
Suvorexant
Veristrat
Bocasan
Toremifene
Icatibant
Fenproporex