Orexin receptor

hypocretin (orexin) receptor 1
Identifiers
SymbolHCRTR1
NCBI gene3061
HGNC4848
OMIM602392
RefSeqNM_001525
UniProtO43613
Other data
LocusChr. 1 p33
Search for
StructuresSwiss-model
DomainsInterPro
hypocretin (orexin) receptor 2
Identifiers
SymbolHCRTR2
NCBI gene3062
HGNC4849
OMIM602393
RefSeqNM_001526
UniProtO43614
Other data
LocusChr. 6 p11-q11
Search for
StructuresSwiss-model
DomainsInterPro
Orexin receptor type 2
Identifiers
SymbolOrexin_rec2
PfamPF03827
InterProIPR004060
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure 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).[1]

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.[2][3]

Several orexin receptor antagonists are in development for potential use in sleep disorders.[4] The first of these, suvorexant, has been on the market in the United States since 2015.[5] There were two orexin agonists under development as of 2019.[6]

  1. ^ Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG (March 2006). "Orexins in the regulation of the hypothalamic-pituitary-adrenal axis". Pharmacological Reviews. 58 (1): 46–57. doi:10.1124/pr.58.1.4. PMID 16507882. S2CID 17941978.
  2. ^ Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, et al. (September 1999). "Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR". British Journal of Pharmacology. 128 (1): 1–3. doi:10.1038/sj.bjp.0702780. PMC 1571615. PMID 10498827.
  3. ^ Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ (January 2004). "Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor". British Journal of Pharmacology. 141 (2): 340–346. doi:10.1038/sj.bjp.0705610. PMC 1574197. PMID 14691055.
  4. ^ Yin J, Mobarec JC, Kolb P, Rosenbaum DM (March 2015). "Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant". Nature. 519 (7542): 247–250. doi:10.1038/nature14035. PMID 25533960. S2CID 4405254.
  5. ^ "Merck's Insomnia Medicine Belsomra C-IV Now Available in US". Sleep Review. 3 February 2015. Retrieved 2019-12-06.
  6. ^ "New Data Presented at World Sleep Congress Demonstrate Early Signs of Efficacy for TAK-925, a Selective Orexin Type-2 Receptor (OX2R) Agonist, in Patients with Narcolepsy Type 1". www.takeda.com. Retrieved 2019-12-06.