Beyond traditional sleeping pills: safety, efficacy and multidisease potential of three approved orexin receptor antagonists.

This is a narrative review aiming to summarize the latest research progress of orexin receptor antagonists in insomnia treatment. To review the latest research progress on orexin receptor antagonists in the treatment of sleep disorders and explore their potential in terms of drug safety, efficacy, addiction risk, and the treatment of insomnia comorbid with psychiatric and neurological disorders. Orexin receptor antagonists bind to orexin receptor-1 (OX1R) and/or orexin receptor-2 (OX2R) receptors, block the orexin-mediated arousal signaling pathway, reduce the body's arousal drive, and thereby improve sleep continuity. Orexin receptor antagonists regulate orexin secretion from the hypothalamus, improving sleep quality and maintaining a normal sleep structure. At present, there are still research gaps in multiple application directions. As a class of agents with unique mechanisms of action, orexin receptor antagonists have promising prospects in the treatment of insomnia. Currently, only three orexin receptor antagonists have been approved for clinical use. Research remains limited, and further exploration is needed in some application areas. As a new class of drugs with a unique mechanism, orexin receptor antagonists show great potential in the treatment of insomnia. Future studies should focus on optimizing their application strategies and addressing current research gaps to provide more comprehensive solutions for sleep disorder management.