(Orexin Antagonism)

The orexins are peptide neuromodulators produced by neurons that are implicated in the regulation of wakefulness and feeding behavior. Synthetic substances that block the G-protein-coupled orexin receptors in the brain hold promise as novel sleep and appetite regulators. Although work had been progressing on potent orexin receptor antagonists in 2002, a major breakthrough came about during 2003 when the first orally active compounds were discovered. One particular substance has been selected for preclinical development based on its overall favorable profile.