Orexin receptor type 1 (OX1R) (OX1R)

Orexin receptor type 1 (OX1R), also known as hypocretin receptor type 1 (HCRTR1), is a G protein-coupled receptor primarily expressed in the central nervous system, particularly in the locus coeruleus and hypothalamus [1, 8]. It is activated by the neuropeptide orexin-A and plays a critical role in regulating the sleep-wake cycle, energy homeostasis, and reward-seeking behavior [2, 3]. In the context of sleep, OX1R works alongside OX2R to promote wakefulness and suppress REM sleep [13, 14]. Dysregulation of the orexin system is linked to narcolepsy, where a loss of orexin-producing neurons leads to excessive daytime sleepiness and cataplexy [2, 13]. Therapeutically, OX1R is a major target for dual orexin receptor antagonists (DORAs) like suvorexant and lemborexant, which are used to treat insomnia by inhibiting wake-promoting signals [4, 14]. Additionally, selective OX1R antagonists are being investigated for their potential in treating substance use disorders and anxiety, as the receptor is heavily involved in the brain's reward and stress-response circuits [8, 11]. Beyond the brain, OX1R is expressed in peripheral tissues like the gastrointestinal tract and reproductive organs, suggesting roles in metabolism and endocrine function [12]. Safety concerns associated with OX1R modulation include daytime somnolence and narcolepsy-like symptoms such as sleep paralysis [15].

Other names

Hypocretin receptor type 1HCRTR1OX1ORXR1OXR1

Antagonism of the orexin receptor type 1 to inhibit wake-promoting and reward-seeking signals.