Orexin receptors

Orexins (hypocretins) are a family of neuropeptides consisting of two members, orexin A and orexin B, which are produced from a common precursor prepro-orexin.  The orexins activate two G-protein-coupled receptors (OX1 and OX2), found predominantly in the hypothalamus.  Orexin A is the selective endogenous agonist for OX1 and blocking this receptor modulates food and water intake.  Orexins are also linked to the regulation of sleep-activity cycles. 

Further reading

Smart et al (1999) Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell line using FLIPR. Br.J.Pharmacol. 128 1 PMID: 10498827

Sutcliffe and de Lecea (2000) The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding. J.Neurosci. Res. 62 161 PMID: 11020209

Scammell and Winrow (2011). Orexin receptors: pharmacology and therapeutic opportunities. Ann. Rev. Pharmacol. Toxicol. 51 243 PMID: 21034217

Inutsuka and Yamanaka (2013) The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions. Front Endocrinol (Lausanne) 4 18 PMID: 23508038

Kukkonen et al (2024) Orexin receptor nomenclature, function and pharmacology.  Pharmacological Reviews June 20 DOI: https://doi.org/10.1124/pharmrev.123.000953

Raymond et al (2025) Found in translation: orexin receptor antagonism for the treatment of opioid use disorder. Transl Psychiatry 15 432 https://doi.org/10.1038/s41398-025-03571-5