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[update].[6]
^Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG (2006). "Orexins in the regulation of the hypothalamic-pituitary-adrenal axis". Pharmacol. Rev. 58 (1): 46–57. doi:10.1124/pr.58.1.4. PMID 16507882. S2CID 17941978.
^Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, Elshourbagy NA, Ellis CE, Middlemiss DN, Brown F (September 1999). "Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR". Br. J. Pharmacol. 128 (1): 1–3. doi:10.1038/sj.bjp.0702780. PMC 1571615. PMID 10498827.
^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): 340–6. doi:10.1038/sj.bjp.0705610. PMC 1574197. PMID 14691055.
^Yin J, Mobarec JC, Kolb P, Rosenbaum DM (December 2014). "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.
^"Merck's Insomnia Medicine Belsomra C-IV Now Available in US". Sleep Review. 3 February 2015. Retrieved 2019-12-06.
^"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.
The orexinreceptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants...
An orexinreceptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one (selective...
Suvorexant is a dual orexinreceptor antagonist (DORA). It acts as a selective dual antagonist of the orexin OX1 and OX2 receptors. The medication has...
The medication is a dual orexinreceptor antagonist (DORA). It acts as a selective dual antagonist of the orexinreceptors OX1 and OX2. Lemborexant has...
Dual orexin receptor antagonists are drugs that block the orexinreceptors OX1 and OX2, hence reducing the wakeful effect of the orexin system and inducing...
cannabinoid receptor 1 (CB1) is colocalized on orexinergic projection neurons in the lateral hypothalamus and many output structures, where the CB1 and orexin receptor...
antidepressants and antihistamines, quetiapine, orexinreceptor antagonists, and melatonin receptor agonists, the orexin antagonist lemborexant and the Z-drug eszopiclone...
colocalized on orexin projection neurons in the lateral hypothalamus and many output structures of the orexin system, where the CB1 and orexinreceptor 1 (OX1)...
an orexin antagonist medication which is under development for the treatment of depression and insomnia. It is a selective antagonist of the orexin OX2...
PMC 3367503. PMID 21729715. Orexinreceptor antagonists a new class of sleeping pill, National Sleep Foundation. "Acetylcholine Receptors". Ebi.ac.uk. Retrieved...
has been found to interact indirectly with the orexin system. It is also likely that an orexinreceptor agonist will be found and developed for the treatment...
their primary neurotransmitter, receptor or method of action. Many drugs act on more than one transmitter or receptor in the brain. Psychoactive drugs...
homodimers, and they also heterodimerized with both orexinreceptors. ... In conclusion, orexinreceptors have a significant propensity to make homo- and...
the orexin OX1 and OX2 receptors. It has a relatively short elimination half-life of 3 to 6 hours. However, it dissociates slowly from the orexin receptors...
Danavorexton (developmental code name TAK-925) is a selective orexin 2 receptor agonist. It is a small-molecule compound and is administered intravenously...
asteroid (biology) Dual orexinreceptor antagonist, an orexin antagonist that inhibits the activity of both OX1 and OX2 receptors (biology) Abbreviation...
Nonproprietary Name; development code TAK-994) is an experimental orexin 2 (OX2) receptor agonist first described in a 2019 patent filed by Takeda Pharmaceutical...
development code ACT-078573, is an orexin antagonist, acting as a competitive antagonist of the OX1 and OX2 orexinreceptors, which was being developed by...
an orexin antagonist medication which is under development for the treatment of insomnia and sleep apnea. It is a dual orexin OX1 and OX2 receptor antagonist...
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