Orexin receptor type 1; Orexin receptor type 2 (OX1R; OX2R)

Orexin receptor type 1 and orexin receptor type 2 (OX1R and OX2R) are members of the class A, rhodopsin-like family of G protein-coupled receptors that are widely expressed in the central and peripheral nervous systems. Their endogenous ligands, orexin-A and orexin-B, are neuropeptides that mediate crucial physiological processes such as maintenance of wakefulness, regulation of feeding behavior, reward seeking, and stress response. OX1R and OX2R are encoded by HCRTR1 and HCRTR2 genes, respectively, and exhibit distinct but overlapping distributions in the brain. Therapeutic antagonists targeting orexin receptors are approved for insomnia; agonists are under development for narcolepsy and other disorders. Dysfunction of the orexin system is implicated in sleep disorders, addiction, neurodegenerative diseases, and certain cancers.

Other names

Hypocretin receptor type 1 (OX1R)Hypocretin receptor type 2 (OX2R)HCRTR1 (gene for OX1R)HCRTR2 (gene for OX2R)

Antagonists block orexin peptide binding, suppressing arousal to treat insomnia. Agonists mimic orexin activity, stimulating wakefulness (potentially for narcolepsy).