Orexin receptor (OXR)

Orexin receptors, comprising the OX1 and OX2 subtypes, are Class A G protein-coupled receptors primarily expressed in the hypothalamus and other brain regions involved in arousal and motivation. They are activated by the endogenous neuropeptides orexin A and orexin B (also known as hypocretins), which are essential for maintaining stable wakefulness and regulating the transition between sleep states. A deficiency in orexin signaling, often due to the loss of orexin-producing neurons, leads to Narcolepsy Type 1, a condition characterized by excessive daytime sleepiness and cataplexy. In contrast, overactivity of the orexin system is implicated in chronic insomnia. Consequently, the orexin system has become a major therapeutic target; dual orexin receptor antagonists (DORAs) such as suvorexant, lemborexant, and daridorexant are FDA-approved for treating insomnia by inhibiting wake-promoting signals. Additionally, orexin receptor agonists are currently under clinical investigation as potential treatments for narcolepsy and other hypersomnia disorders to restore normal arousal levels.

Other names

Hypocretin receptorOX1ROX2RHCRTR1HCRTR2Orexin receptor type 1Orexin receptor type 2OX receptor

Orexin receptor antagonism (blocking wake-promoting signals to treat insomnia) and orexin receptor agonism (mimicking endogenous orexin to treat narcolepsy).