Orexin receptor

The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX₁ and OX₂, each encoded by a different gene (HCRTR1, HCRTR2).

Both orexin receptors exhibit a similar pharmacology – the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 5- to 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors.

Several orexin receptor antagonists are in development for potential use in sleep disorders. The first of these, suvorexant, has been on the market in the United States since 2015. There were two orexin agonists under development as of 2019.