Orexin receptor (OXR)

The Orexin receptor system, comprising Orexin receptor type 1 (OX1R) and Orexin receptor type 2 (OX2R), is a critical regulator of the sleep-wake cycle and arousal [UniProt, 2023]. These G protein-coupled receptors are primarily activated by the neuropeptides Orexin-A and Orexin-B, which are synthesized in the lateral hypothalamus [StatPearls, 2023]. In the central nervous system, orexin signaling promotes wakefulness and suppresses REM sleep; a profound loss of orexin-producing neurons leads to Narcolepsy Type 1 [PubMed, 2020]. Conversely, overactivity of this pathway is implicated in the pathophysiology of insomnia, making these receptors prime targets for sedative-hypnotic drugs [Nature Reviews Drug Discovery, 2022]. Current therapeutic interventions include dual orexin receptor antagonists (DORAs) such as suvorexant, lemborexant, and daridorexant, which facilitate sleep by blocking the wake-promoting signals of the orexin system [FDA, 2022]. Emerging research is also focusing on orexin receptor agonists as potential treatments for narcolepsy and other hypersomnia disorders to restore normal arousal levels [Journal of Medicinal Chemistry, 2021].

Other names

Hypocretin receptorOX1ROX2RHCRTR1HCRTR2Orexin-1 receptorOrexin-2 receptor

Dual orexin receptor antagonism (DORA), Selective orexin receptor antagonism (SORA), Orexin receptor agonism