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Orexin receptor

hypocretin (orexin) receptor 1
Identifiers
Symbol HCRTR1
Entrez 3061
HUGO 4848
OMIM 602392
RefSeq NM_001525
UniProt O43613
Other data
Locus Chr. 1 p33
hypocretin (orexin) receptor 2
Identifiers
Symbol HCRTR2
Entrez 3062
HUGO 4849
OMIM 602393
RefSeq NM_001526
UniProt O43614
Other data
Locus Chr. 6 p11-q11
Orexin receptor type 2
Identifiers
Symbol Orexin_rec2
Pfam PF03827
InterPro IPR004060

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 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. Only the crystal structure of OX2 is known.

Several drugs acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. No non-peptide agonists are yet available, although synthetic Orexin-A polypeptide has been made available as a nasal spray and tested on monkeys. Several non-peptide antagonists are in development however; SB-649,868 by GlaxoSmithKline for sleep disorders is a non-selective orexin receptor antagonist. Another dual orexin antagonist, almorexant (ACT-078573) by Actelion, was abandoned because of side effects. A third entry is Merck's suvorexant (Belsomra), which has recently been approved for use. A new antagonist compound, ACT-462206, was recently studied in humans.


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