Orexin receptor antagonists are clinically useful for treating insomnia, but thorough blockade of orexin signaling could cause narcolepsy-like symptoms.
Orexin receptor antagonists may have therapeutic value in the treatment of insomnia, yet the use of this class of drugs in the treatment of sleep disturbances following adolescent alcohol exposure has not been studied.
The disposition and metabolism of lemborexant, a novel dual orexin receptor antagonist currently under development as a therapeutic agent for insomnia disorder, were evaluated after a single oral administration of [<sup>14</sup>C]lemborexant in Sprague-Dawley rats (10 mg/kg) and cynomolgus monkeys (3 mg/kg).
The aim of this study was to investigate the safety and efficacy of a new hypnotic agent, suvorexant, a dual orexin receptor antagonist, for insomnia in suspected OSA patients during in-laboratory PSG.
This first multicenter, randomized, double-blind study investigated the effects of suvorexant, a reversible dual orexin receptor antagonist, on nighttime blood pressure (BP) in patients with insomnia and hypertension.
Suvorexant, an orexin receptor antagonist used for insomnia, has been shown to have a preventive effect on delirium in a randomized placebo-controlled trial.
Central actions of orexin, mediated by orexin-1 and orexin-2 receptors, play a crucial role in the maintenance of wakefulness; accordingly, excessive activation of the orexin system causes insomnia.
Targeting the orexin receptor system for treatment of insomnia offers an additional and alternative pharmacological approach to more common gamma aminobutyric acid agonist sedative hypnotic treatment.
Hyper-activation of the orexin system also causes sleep disturbances, such as insomnia, and hence, suvorexant, an orexin receptor antagonist, has been clinically used to treat insomnia.
Available guidelines and reviews are summarized and recommendations formulated regarding the use of benzodiazepines and hypnotic benzodiazepine receptor agonists, melatonin and melatonin receptor agonists, sedating antidepressants, antipsychotics and antihistamines, and orexin receptor antagonists in insomnia disorder.
Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and benzodiazepines.
It was shown that <b>L4</b> was the most potent antagonistic ligand to orexin A and displayed an IC<sub>50</sub> of 2.2 µM, offering some promise mainly for the treatment of insomnia.
Approved U.S. Food and Drug Administration medications to treat insomnia include the following: benzodiazepines (estazolam, flurazepam, temazepam, triazolam, and quazepam), non-benzodiazepine hypnotics (eszopiclone, zaleplon, zolpidem), the melatonin receptor agonist ramelteon, the antidepressant doxepin, and the orexin receptor antagonist suvorexant.
In an ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX<sub>2</sub>R subtype and culminating in the discovery of 23, a highly potent, OX<sub>2</sub>R-selective molecule that exhibited a promising in vivo profile.