オレキシン受容体、オレキシンレセプター

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/04/19 15:47:26」(JST)

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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 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors.^[2]

Several orexin receptor antagonists are in development for potential use in sleep disorders. Only the crystal structure of OX2 is known.^[3]

Synthetic ligands

Several drugs^[4] 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 neuropeptide agonists are yet available, although synthetic Orexin-A polypeptide has been made available as a nasal spray and tested on monkeys. One non-peptide antagonist is currently available in the U.S., Merck's suvorexant (Belsomra),^[5]; two additional agents are in development: SB-649,868 by GlaxoSmithKline, for sleep disorders, and ACT-462206, currently in human clinical trials.^[6]. Another drug in development, almorexant (ACT-078573) by Actelion, was abandoned due to adverse effects.

Most ligands acting on the orexin system so far are polypeptides modified from the endogenous agonists Orexin-A and Orexin-B, however there are some subtype-selective non-peptide antagonists available for research purposes.

SB-334,867 – selective OX₁ antagonist
SB-408,124 – selective OX₁ antagonist
TCS-OX2-29 – selective OX₂ antagonist
EMPA (N-Ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) – selective OX₂ antagonist
RTIOX-276 – selective OX₁ antagonist

References

^ 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.
^ 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.
^ 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: 247–250. doi:10.1038/nature14035. PMID 25533960.
^ Heifetz A, Morris GB, Biggin PC, Barker O, Fryatt T, Bentley J, Hallett D, Manikowski DP, Pal S, Reifegerste R, Slack M, Law R (2012). "Study of Human Orexin-1 and -2 G-Protein-Coupled Receptors with Novel and Published Antagonists by Modeling, Molecular Dynamics Simulations, and Site-Directed Mutagenesis". Biochemistry. 51 (15): 3178–3197. doi:10.1021/bi300136h. PMID 22448975.
^ Baxter CA, Cleator ED, Karel MJ, Edwards JS, Reamer RA, Sheen FJ, Stewart GW, Strotman NA, Wallace DJ (2011). "The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder". Organic Process Research & Development. 15 (2): 367–375. doi:10.1021/op1002853.
^ Hoch M, van Gorsel H, van Gerven J, Dingemanse J (Sep 2014). "Entry-into-humans study with ACT-462206, a novel dual orexin receptor antagonist, comparing its pharmacodynamics with almorexant". J Clin Pharmacol. 54: 979–86. doi:10.1002/jcph.297. PMID 24691844.

External links

"Orexin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Orexin Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro IPR004060

This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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1. Treatment of insomnia in adults
2. 成人におけるナルコレプシーの臨床的特徴および診断 clinical features and diagnosis of narcolepsy in adults
3. 睡眠の質および睡眠の構造に対する薬剤の効果 the effects of medications on sleep quality and sleep architecture
4. 肥満の病因 pathogenesis of obesity
5. 入院中の睡眠不足：要因と介入 poor sleep in the hospital contributing factors and interventions

English Journal

Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons.

Ardianto C1, Yonemochi N1, Yamamoto S1, Yang L1, Takenoya F2, Shioda S3, Nagase H4, Ikeda H5, Kamei J1.
Neuroscience.Neuroscience.2016 Apr 21;320:183-93. doi: 10.1016/j.neuroscience.2016.02.002. Epub 2016 Feb 6.
The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3mg/kg, s.c.) and selective μ-
PMID 26855191

Involvement of the orexin/hypocretin system in the pharmacological effects induced by Δ(9) -tetrahydrocannabinol.

Flores Á1, Julià-Hernández M1, Maldonado R1, Berrendero F1.
British journal of pharmacology.Br J Pharmacol.2016 Apr;173(8):1381-92. doi: 10.1111/bph.13440. Epub 2016 Mar 3.
BACKGROUND AND PURPOSE: Anatomical, biochemical and pharmacological evidence suggest the existence of a crosstalk between the orexinergic and endocannabinoid systems. While the orexin receptor 1 (OX1 receptor) modulates the reinforcing properties of cannabinoids, the participation of orexins in the
PMID 26799708

The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice.

Lopez MF1, Moorman DE2, Aston-Jones G3, Becker HC4.
Brain research.Brain Res.2016 Apr 1;1636:74-80. doi: 10.1016/j.brainres.2016.01.049. Epub 2016 Feb 4.
The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivat
PMID 26851547

Japanese Journal

抗不安薬 : ベンゾジアゼピン (特集痛み診療の場で使用される種々の非オピオイド性鎮痛薬の現況と課題)

麻酔 = The Japanese journal of anesthesiology : 日本麻酔科学会準機関誌 67(7), 730-734, 2018-07
NAID 40021627918

Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors

Nature communications 9, 1576, 2018-04
NAID 120006478282

スボレキサント(ベルソムラ)追加・変更投与が有効であった睡眠障害症例

東都医療大学紀要 8(1), 41-44, 2018-03
NAID 40021631077

「オレキシンレセプター」

Orexin receptor type 2
Identifiers
Symbol	Orexin_rec2
Pfam	PF03827
InterPro	IPR004060
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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

hypocretin (orexin) receptor 1
Identifiers
Symbol	HCRTR1
Entrez	3061
HUGO	4848
OMIM	602392
RefSeq	NM_001525
UniProt	O43613
Other data
Locus	Chr. 1 p33

　　[★]

英: orexin receptor
関: オレキシン受容体

[pmid16507882-1] 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.

[pmid10498827-2] 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.

[nature-3] 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: 247–250. doi:10.1038/nature14035. PMID 25533960.

[Heifetz_2012-4] Heifetz A, Morris GB, Biggin PC, Barker O, Fryatt T, Bentley J, Hallett D, Manikowski DP, Pal S, Reifegerste R, Slack M, Law R (2012). "Study of Human Orexin-1 and -2 G-Protein-Coupled Receptors with Novel and Published Antagonists by Modeling, Molecular Dynamics Simulations, and Site-Directed Mutagenesis". Biochemistry. 51 (15): 3178–3197. doi:10.1021/bi300136h. PMID 22448975.

[Baxter_2011-5] Baxter CA, Cleator ED, Karel MJ, Edwards JS, Reamer RA, Sheen FJ, Stewart GW, Strotman NA, Wallace DJ (2011). "The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder". Organic Process Research & Development. 15 (2): 367–375. doi:10.1021/op1002853.

[6] Hoch M, van Gorsel H, van Gerven J, Dingemanse J (Sep 2014). "Entry-into-humans study with ACT-462206, a novel dual orexin receptor antagonist, comparing its pharmacodynamics with almorexant". J Clin Pharmacol. 54: 979–86. doi:10.1002/jcph.297. PMID 24691844.

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orexin receptor