Iguratimod orexins are related to hypocretins and were first described by Sakurai et al.. Orexins have been demonstrated in the lateral hypothalamic region, an area of the brain closely associated with the regulation of behaviour. A strong indication of the role of orexin-positive neurons in feeding is that genetic ablation of orexigenic neurons results in narcolepsy, hyperphagia and obesity. Orexin-1 receptor was the first of the two orexin receptors to be discovered and binds orexin-A with a much higher affinity compared to orexin B. The human OX1R protein consists of 425 amino acids and seven putative transmembrane helices. OX2R consists of 444 amino acids and has equal affinities for both orexin A and B ligands. OX2R shares about 64% amino acid identity with OX1R. In addition, OX1R is more selective for orexin A and usually coupled to the Gq subclass of G proteins while OX2R can couple to either Gq and/or Gi/o subset of G proteins. The binding of OX1R and OX2R to either orexin A or B causes intracellular influx of Ca2+ resulting in increased concentration of intracellular Ca2+. OX1R and OX2R are present in the lateral hypothalamic area, which is rich in orexin-positive nerves. In the hypothalamic region, OX1R mRNA is located mainly in the dorsomedial area of the ventromedial hypothalamic nucleus and the anterior hypothalamic territory, whereas, OX2R mRNA is observed in several hypothalamic nuclei including the arcuate nucleus, posteroventricular nucleus, LHA, and tuberomammilary bodies. The localization of orexin receptors to these hypothalamic nuclei supports the purported function of orexins on the regulation of feeding, since food intake and appetite are regulated by these cortical regions. The role of VMH in the regulation of food intake is very strong because the selective ablation of VMH results in obesity. Moreover, expression of OX1R mRNA has been demonstrated in many other parts of the brain, including the hippocampus, locus coeruleus and raphe nuclei.The localization of OX1R mRNA in these cortical regions, which has large quantities of adrenergic and serotonergic neurotransmitters Rucaparib Camsylate suggests that orexins may also play an important role in the regulation of serotonergic as well as adrenergic systems.