Orexin receptors (OXRs) are class A G-protein coupled receptors (GPCRs). The importance of the OXR system in various physiological functions and its role in neurological disorders and cancer have been the subject of numerous studies . The endogenous OXR ligands, OX-A and OX-B, which are almost exclusively expressed in the hypothalamus, bind to OX1R and OX2R with different selectivities, such that OX-A is non-selective, whereas OX-B shows preferential binding to OX2R. Each OXR subtype showed distinct expression patterns in the central nervous system. For example, the prefrontal cortex showed predominant expression of the OX1R, whereas the nucleus accumbens possessed only the OX2R (3). While the OX2R has been reported to modulate the sleep-wake rhythm and OX2R agonism increased wakefulness in narcoleptic mice and human , the OX1R has a major impact on emotional behavior and OX1R antagonism influenced cocaine-seeking behavior in mice . Interestingly, OXR expression has been demonstrated in human adrenals , where they stimulate glucocorticoid secretion. In adrenocortical tumors, OXR are upregulated and orexins stimulate tumor proliferation, indicating an autocrine-paracrine mechanism for the regulation of adrenal tumor growth . More recent work has shown, that various tumor cell lines, including colorectal, pancreatic and liver cancer cell lines, express OX1R and tumor growth of pancreatic AsPC-1 tumor xenografts in nude mice was inhibited by treatment with OX-A . Therefore, the OX1R represents an interesting target for diagnostic and therapeutic approaches related to brain disorders and cancer.