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 | ||||||||
|
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| Available protein structures: | |
|---|---|
| Pfam | structures |
| PDB | RCSB PDB; PDBe; PDBj |
| PDBsum | structure summary |
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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