Orexin neuropeptide (null)

Orexin neuropeptides (orexin-A and orexin-B, also called hypocretins) are produced by a small population of neurons in the hypothalamus and signal through two G protein-coupled receptors: OX1R and OX2R. They coordinate multiple physiological roles, including maintenance of wakefulness, stimulating arousal, regulating food intake and energy expenditure, and modulating reward and mood-related pathways. Loss of orexin leads to narcolepsy with cataplexy, marking these peptides and their receptors as critical therapeutic targets for sleep disorders. Orexin signaling also modulates neuroendocrine stress responses, promotes brown fat thermogenesis, and induces apoptosis in several cancer cell lines, suggesting wider potential as a therapeutic target in neuroinflammatory, metabolic, and neoplastic disorders as well.

Other names

hypocretinHCRTorexin-Aorexin-B

Antagonists (block OX1R and OX2R, reducing wakefulness, treating insomnia); Selective antagonism (SORA1 or SORA2, targeting specific orexin receptor subtype for selected indications); Dual antagonism (DORA, simultaneous OX1R/OX2R blockade, for broader sleep benefit); Agonists or activation increasing alertness, energy expenditure, or promoting feeding (preclinical context)