オピエート受容体、アヘン受容体

関: opioid receptor

WordNet

a narcotic drug that contains opium or an opium derivative
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

アヘン剤,鎮静剤 / (…にとって)鎮静させるもの《+『to』+『名』》 / アヘンを用いた;鎮静の
=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）』「2016/10/23 15:41:42」(JST)

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An animated view of the human k-opioid receptor in complex with the antagonist JDTic.

Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands.^[1]^[2]^[3] The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). Opioid receptors are distributed widely in the brain, and are found in the spinal cord and digestive tract.

Discovery

By the mid-1960s, it had become apparent from pharmacologic studies that opiate drugs were likely to exert their actions at specific receptor sites, and that there were likely to be multiple such sites.^[4] Early studies had indicated that opiates appeared to accumulate in the brain.^[5] The receptors were first identified as specific molecules through the use of binding studies, in which opiates that had been labeled with radioisotopes were found to bind to brain membrane homogenates. The first such study was published in 1971, using ³H-levorphanol.^[6] In 1973, Candace Pert and Solomon H. Snyder published the first detailed binding study of what would turn out to be the μ opioid receptor, using ³H-naloxone.^[7] That study has been widely credited as the first definitive finding of an opioid receptor, although two other studies followed shortly after.^[8]^[9]

Purification

Purification of the receptor further verified its existence. The first attempt to purify the receptor involved the use of a novel opioid receptor antagonist called chlornaltrexamine that was demonstrated to bind to the opioid receptor.^[10] Caruso later purified the detergent-extracted component of rat brain membrane that eluted with the specifically bound ³H-chlornaltrexamine.^[11]

Major subtypes

There are four major subtypes of opioid receptors:^[12]

Receptor	Subtypes	Location^[13]^[14]	Function^[13]^[14]
delta (δ) DOR OP₁ ^(I)	δ₁,^[15] δ₂	brain pontine nuclei amygdala olfactory bulbs deep cortex peripheral sensory neurons	analgesia antidepressant effects convulsant effects physical dependence may modulate μ-opioid receptor-mediated respiratory depression
kappa (κ) KOR OP₂ ^(I)	κ₁, κ₂, κ₃	brain hypothalamus periaqueductal gray claustrum spinal cord substantia gelatinosa peripheral sensory neurons	analgesia anticonvulsant effects depression dissociative/hallucinogenic effects diuresis dysphoria miosis neuroprotection sedation stress
mu (μ) MOR OP₃ ^(I)	μ₁, μ₂, μ₃	brain cortex (laminae III and IV) thalamus striosomes periaqueductal gray rostral ventromedial medulla spinal cord substantia gelatinosa peripheral sensory neurons intestinal tract	μ₁: analgesia physical dependence μ₂: respiratory depression miosis euphoria reduced GI motility physical dependence μ₃: possible vasodilation
Nociceptin receptor NOR OP₄	ORL₁	brain cortex amygdala hippocampus septal nuclei habenula hypothalamus spinal cord	anxiety depression appetite development of tolerance to μ-opioid agonists
zetta (ζ) ZOR		heart liver skeletal muscle kidney brain pancreas fetal tissue liver kidney	tissue growth embryonic development regulation of cancer cell proliferation

(I). Name based on order of discovery

Evolution

The opioid receptor family originated from two duplication events of a single ancestral opioid receptor early in vertebrate evolution. Phylogenetic analysis demonstrates that the family of opioid receptors was already present at the origin of jawed vertebrates over 450 million years ago. In humans, this paralogon resulting from a double tetraploidization event resulted in the receptor genes being located on chromosomes 1, 6, 8, and 20. Tetraploidization events often result in loss of one more or the duplicated genes, but in this case, nearly all species retain all four opioid receptors, indicating important and specific function. The receptor families delta, kappa, and mu demonstrate 55–58% identity to one another, and a 48–49% homology to the nociceptin receptor. Taken together, this indicates that the NOP receptor gene, OPRL1, has equal evolutionary origin, but a higher mutation rate, than the other receptor genes.^[16]

The endogenous opioid system is thought to be important in mediating complex social behaviors involved in the formation of stable, emotionally committed relationships. Social attachment was demonstrated to be mediated by the opioid system through experiments administering morphine and naltrexone, an opioid agonist and antagonist, to juvenile guinea pigs. The agonist decreased the preference of the juvenile to be near the mother and reduced distress vocalization whereas the antagonist had the opposite effects. Experiments were corroborated in dogs, chicks, and rats confirming the evolutionary importance of opioid signaling in these behaviors.^[17] Researchers have also found that systemic naltrexone treatment of female prairie voles during initial exposure to a male reduced subsequent mating bouts and nonsexual socialization with this familiar partner, when a choice test including a novel male was performed afterwards. This points to a role for opioid receptors in mating behaviors.^[18]

There is evidence that human specific cognitive traits rely not on coding differences for the receptors or ligands, which display 99% homology with primates, but instead due to regulatory changes in expression levels that are specifically selected for.^[19]^[20]

Naming

The receptors were named using the first letter of the first ligand that was found to bind to them. Morphine was the first chemical shown to bind to mu receptors. The first letter of the drug morphine is m, rendered as the corresponding Greek letter μ. In similar manner, a drug known as ketocyclazocine was first shown to attach itself to κ receptors,^[21] while the δ receptor was named after the mouse vas deferens tissue in which the receptor was first characterised.^[22] An additional opioid receptor was later identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or ORL1 (opiate receptor-like 1).

The opioid receptor types are ~70% identical with differences located at N and C termini. The μ receptor is perhaps the most important. It is thought that the G protein binds to the third intracellular loop of the opioid receptors. Both in mice and humans, the genes for the various receptor subtypes are located on different chromosomes.

Separate subtypes have been identified in human tissue. Research has so far failed to identify the genetic evidence of the subtypes, and it is thought that they arise from post-translational modification of cloned receptor types.^[23]

An IUPHAR subcommittee^[24]^[25] has recommended that appropriate terminology for the 3 classical (μ, δ, κ) receptors, and the non-classical (nociceptin) receptor, should be MOP, DOP, KOP and NOP respectively.

Additional receptors

Sigma (σ) receptors were once considered to be opioid receptors due to the antitussive actions of many opioid drugs' being mediated via σ receptors, and the first selective σ agonists being derivatives of opioid drugs (e.g., allylnormetazocine). However, σ receptors were found to not be activated by endogenous opioid peptides, and are quite different from the other opioid receptors in both function and gene sequence, so they are now not usually classified with the opioid receptors.

The existence of further opioid receptors (or receptor subtypes) has also been suggested because of pharmacological evidence of actions produced by endogenous opioid peptides, but shown not to be mediated through any of the four known opioid receptor subtypes. The existence of receptor subtypes or additional receptors other than the classical opioid receptors (μ, δ, κ) has been based on limited evidence, since only three genes for the three main receptors have been identified.^[26]^[27]^[28]^[29] The only one of these additional receptors to have been definitively identified is the zeta (ζ) opioid receptor, which has been shown to be a cellular growth factor modulator with met-enkephalin being the endogenous ligand. This receptor is now most commonly referred to as the opioid growth factor receptor (OGFr).^[30]^[31]

ε opioid receptor

Another postulated opioid receptor is the ε opioid receptor. The existence of this receptor was suspected after the endogenous opioid peptide beta-endorphin was shown to produce additional actions that did not seem to be mediated through any of the known opioid receptors.^[32]^[33] Activation of this receptor produces strong analgesia and release of met-enkephalin, and a number of widely used opioid agonists such as the μ agonist etorphine and the κ agonist bremazocine have been shown to act as agonists for this effect (even in the presence of antagonists to their more well known targets),^[34] while buprenorphine has been shown to act as an epsilon antagonist. Several selective agonists and antagonists are now available for the putative epsilon receptor,^[35]^[36] however efforts to locate a gene for this receptor have been unsuccessful, and epsilon-mediated effects were absent in μ/δ/κ "triple knockout" mice,^[37] suggesting the epsilon receptor is likely to be either a splice variant derived from alternate post-translational modification, or a heteromer derived from hybridization of two or more of the known opioid receptors.

Pathology

Some forms of mutations in δ-opioid receptors have resulted in constant receptor activation.^[38]

Protein–protein interactions

Receptor heteromers

δ-κ^[39]
δ-μ
κ-μ
μ-ORL1
δ-CB1
μ-CB1
δ-α2A
δ-β2
κ-β2
μ-α2A
δ-CXCR4
δ-SNSR4
κ-APJ
μ-CCR5
μ1D-GRPR
μ-mGlu5
μ-5-HT1A
μ-NK1
μ-sst2A

References

^ Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, Hamon M (December 1996). "International Union of Pharmacology. XII. Classification of opioid receptors" (PDF). Pharmacol. Rev. 48 (4): 567–592. PMID 8981566.
^ Janecka A, Fichna J, Janecki T (2004). "Opioid receptors and their ligands". Curr. Top. Med. Chem. 4 (1): 1–17. doi:10.2174/1568026043451618. PMID 14754373.
^ Waldhoer M, Bartlett SE, Whistler JL (2004). "Opioid receptors". Annu. Rev. Biochem. 73: 953–990. doi:10.1146/annurev.biochem.73.011303.073940. PMID 15189164.
^ Martin, W. R. (December 1967). "Opioid antagonists". Pharmacol. Rev. 19 (4): 463–521. PMID 4867058. Retrieved December 29, 2013.
^ Ingoglia NA, Dole VP (1970). "Localization of d and l-methadone after intraventricular injection into rat brains.". J. Pharmacol. Exp. Ther. 175 (1): 84–87. PMID 5471456.
^ Goldstein A, Lowney LI, Pal BK (August 1971). "Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain". Proc. Natl. Acad. Sci. U.S.A. 68 (8): 1742–7. doi:10.1073/pnas.68.8.1742. PMC 389284. PMID 5288759.
^ Pert CB, Snyder SH (March 1973). "Opiate receptor: demonstration in nervous tissue". Science. 179 (4077): 1011–4. doi:10.1126/science.179.4077.1011. PMID 4687585.
^ Terenius L (1973). "Stereospecific interaction between narcotic analgesics and a synaptic plasm a membrane fraction of rat cerebral cortex". Acta Pharmacol. Toxicol. (Copenh.). 32 (3): 317–20. doi:10.1111/j.1600-0773.1973.tb01477.x. PMID 4801733.
^ Simon EJ, Hiller JM, Edelman I (July 1973). "Stereospecific binding of the potent narcotic analgesic (3H) Etorphine to rat-brain homogenate". Proc. Natl. Acad. Sci. U.S.A. 70 (7): 1947–9. doi:10.1073/pnas.70.7.1947. PMC 433639. PMID 4516196.
^ Caruso TP; AE Takemori; DL Larson; PS Portoghese (April 1979). "Chloroxymorphamine, an opioid receptor site-directed alkylating agent having narcotic agonist activity". Science. 204 (4390): 316–8. doi:10.1126/science.86208. PMID 86208.
^ Caruso TP; DL Larson; PS Portoghese; AE Takemori (December 1980). "Isolation of selective 3H-chlornaltrexamine-bound complexes, possible opioid receptor components in brains of mice". Life Sciences. 27 (22): 2063–9. doi:10.1016/0024-3205(80)90485-3. PMID 6259471.
^ Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006). "75 years of opioid research: the exciting but vain quest for the Holy Grail". Br. J. Pharmacol. 147 Suppl 1 (Suppl 1): S153–62. doi:10.1038/sj.bjp.0706435. PMC 1760732. PMID 16402099.
^ ^a ^b Stein C, Schäfer M, Machelska H (August 2003). "Attacking pain at its source: new perspectives on opioids". Nat. Med. 9 (8): 1003–8. doi:10.1038/nm908. PMID 12894165.
^ ^a ^b Fine PG, Portenoy RK (2004). "Chapter 2: The Endogenous Opioid System" (PDF). A Clinical Guide to Opioid Analgesia. McGraw Hill.
^ Portoghese PS, Lunzer MM (2003). "Identity of the putative delta1-opioid receptor as a delta-kappa heteromer in the mouse spinal cord". Eur. J. Pharmacol. 467 (1-3): 233–4. doi:10.1016/s0014-2999(03)01599-1. PMID 12706480.
^ Stevens CW (2009). "The evolution of vertebrate opioid receptors". Front Biosci (Landmark Ed). 14: 1247–69. PMC 3070387. PMID 19273128.
^ Furay AR, Neumaier JF (October 2011). "Opioid receptors: binding that ties". Neuropsychopharmacology. 36 (11): 2157–8. doi:10.1038/npp.2011.147. PMC 3176578. PMID 21918519.
^ Burkett JP, Spiegel LL, Inoue K, Murphy AZ, Young LJ (October 2011). "Activation of μ-opioid receptors in the dorsal striatum is necessary for adult social attachment in monogamous prairie voles". Neuropsychopharmacology. 36 (11): 2200–10. doi:10.1038/npp.2011.117. PMC 3176565. PMID 21734650.
^ Cruz-Gordillo P, Fedrigo O, Wray GA, Babbitt CC (2010). "Extensive changes in the expression of the opioid genes between humans and chimpanzees". Brain Behav. Evol. 76 (2): 154–62. doi:10.1159/000320968. PMID 21079395.
^ Rockman MV, Hahn MW, Soranzo N, Zimprich F, Goldstein DB, Wray GA (December 2005). "Ancient and recent positive selection transformed opioid cis-regulation in humans". PLoS Biol. 3 (12): e387. doi:10.1371/journal.pbio.0030387. PMC 1283535. PMID 16274263.
^ Aggrawal, Anil (May 1, 1995). "Opium: the king of narcotics". Opioids: past, present and future. BLTC Research. Archived from the original on May 26, 2012. Retrieved December 29, 2013.
^ Lord JA, Waterfield AA, Hughes J, Kosterlitz HW. Nature. 1977; 267:495–499.
^ Lemke, Thomas L.; Williams, David H.; Foye, William O. (2002). "Opioid Analgesics; Fries, DS". Foye's principles of medicinal chemistry. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.
^ Girdlestone D (October 2000). "Opioid receptors; Cox BM, Chavkin C, Christie MJ, Civelli O, Evans C, Hamon MD, et al.". The IUPHAR Compendium of Receptor Characterization and Classification (2nd ed.). London: IUPHAR Media. pp. 321–333.
^ "Opioid receptors". IUPHAR Database. International Union of Pharmacology (2008-08-01).
^ Dietis N, Rowbotham D, Lambert D (May 2011). "Opioid receptor subtypes: fact or artifact?". B.J.A. 107 (1): 8–18. doi:10.1093/bja/aer115. PMID 21613279.
^ Grevel J, Yu V, Sadée W (May 1985). "Characterization of a labile naloxone binding site (lambda site) in rat brain". J. Neurochem. 44 (5): 1647–56. doi:10.1111/j.1471-4159.1985.tb08808.x. PMID 2985759.
^ Mizoguchi H, Narita M, Nagase H, Tseng LF (October 2000). "Activation of G-proteins in the mouse pons/medulla by beta-endorphin is mediated by the stimulation of mu- and putative epsilon-receptors". Life Sci. 67 (22): 2733–43. doi:10.1016/S0024-3205(00)00852-3. PMID 11105989.
^ Wollemann M, Benyhe S (June 2004). "Non-opioid actions of opioid peptides". Life Sci. 75 (3): 257–70. doi:10.1016/j.lfs.2003.12.005. PMID 15135648.
^ Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (February 2000). "Cloning, sequencing, chromosomal location, and function of cDNAs encoding an opioid growth factor receptor (OGFr) in humans". Brain Res. 856 (1–2): 75–83. doi:10.1016/S0006-8993(99)02330-6. PMID 10677613.
^ Zagon IS, Verderame MF, McLaughlin PJ (February 2002). "The biology of the opioid growth factor receptor (OGFr)". Brain Res. Brain Res. Rev. 38 (3): 351–76. doi:10.1016/S0165-0173(01)00160-6. PMID 11890982.
^ Wüster M, Schulz R, Herz A (December 1979). "Specificity of opioids towards the mu-, delta- and epsilon-opiate receptors". Neurosci. Lett. 15 (2–3): 193–8. doi:10.1016/0304-3940(79)96112-3. PMID 231238.
^ Schulz R, Wüster M, Herz A (March 1981). "Pharmacological characterization of the epsilon-opiate receptor". J. Pharmacol. Exp. Ther. 216 (3): 604–6. PMID 6259326.
^ Narita, Minoru; Tseng, Leon F. (1998). "Evidence for the Existence of the β-Endorphin-Sensitive "ε-Opioid Receptor" in the Brain: The Mechanisms of ε-Mediated Antinociception". The Japanese Journal of Pharmacology. 76 (3): 233–253. doi:10.1254/jjp.76.233. ISSN 0021-5198. PMID 9593217.
^ Fujii H, Narita M, Mizoguchi H, Murachi M, Tanaka T, Kawai K, Tseng LF, Nagase H (August 2004). "Drug design and synthesis of epsilon opioid receptor agonist: 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid receptor". Bioorg. Med. Chem. 12 (15): 4133–45. doi:10.1016/j.bmc.2004.05.024. PMID 15246090.
^ Fujii H, Nagase H (2006). "Rational drug design of selective epsilon opioid receptor agonist TAN-821 and antagonist TAN-1014". Curr. Med. Chem. 13 (10): 1109–18. doi:10.2174/092986706776360851. PMID 16719773.
^ Contet C, Matifas A, Kieffer BL (May 2004). "No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse". Eur. J. Pharmacol. 492 (2–3): 131–6. doi:10.1016/j.ejphar.2004.03.056. PMID 15178356.
^ Befort K, Zilliox C, Filliol D, Yue S, Kieffer BL (June 1999). "Constitutive activation of the delta opioid receptor by mutations in transmembrane domains III and VII". J. Biol. Chem. 274 (26): 18574–81. doi:10.1074/jbc.274.26.18574. PMID 10373467.
^ Fujita W, Gomes I, Devi LA (2014). "Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10". Br. J. Pharmacol. 171 (18): 4155–76. doi:10.1111/bph.12798. PMC 4241085. PMID 24916280.

External links

Opioid Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
"Opioid Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Corbett A, McKnight S, Henderson G. "Opioid Receptors". BLTC Research. Retrieved 2008-03-21.
Lomize A, Lomize M, Pogozheva I. "Orientations of Proteins in Membranes (OPM) database". University of Michigan. Retrieved 2008-03-21.
- "Mu-opioid receptor model (inactive state) with antagonist". Retrieved 2008-03-21.
- "Mu-opioid receptor model in active state with agonist". Retrieved 2008-03-21.
Guzman F. "Video lectures on opioid receptors". Pharmacology Corner. Retrieved 2012-07-30.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. オピオイド乱用および依存：概要および患者評価 opioid abuse and dependence overview and patient evaluation
2. 慢性疼痛の治療の概要 overview of the treatment of chronic pain
3. オピオイドの使用および依存の治療 treatment of opioid use and dependence
4. 危篤状態の成人患者における疼痛管理 pain control in the critically ill adult patient
5. 成人におけるオピオイド中毒 opioid intoxication in adults

English Journal

The Epigenetic Regulation of the Opioid System: New Individualized Prompt Prevention and Treatment Strategies.

Muñoa I1, Urizar I1, Casis L1, Irazusta J1, Subirán N1.
Journal of cellular biochemistry.J Cell Biochem.2015 Nov;116(11):2419-26. doi: 10.1002/jcb.25222.
The most well-known physiological effect associated with opiod system is their efficacy in pain reduction or analgesia, although their effect on a variety of other physiological and physiophological functions has become apparent in recent years. This review is an attempt to clarify in more detail th
PMID 25974312

Opioid-induced constipation.

Gyawali B1, Hayashi N, Tsukuura H, Honda K, Shimokata T, Ando Y.
Scandinavian journal of gastroenterology.Scand J Gastroenterol.2015 Nov;50(11):1331-8. doi: 10.3109/00365521.2015.1054423. Epub 2015 Jun 10.
Opioid-induced constipation (OIC) is a very troublesome, difficult to manage and a nearly universal complication of chronic opioid use to control pain associated with advanced illness. Some studies have reported that OIC is so intolerable in some patients that they skip their opioid medications and
PMID 26061717

Effects of remifentanil on esophageal motility: a double-blind, randomized, cross-over study in healthy volunteers.

Savilampi J1, Magnuson A1, Ahlstrand R1.
Acta anaesthesiologica Scandinavica.Acta Anaesthesiol Scand.2015 Oct;59(9):1126-36. doi: 10.1111/aas.12534. Epub 2015 Apr 29.
BACKGROUND: Recent studies have shown that remifentanil increases the risk of aspiration and induces subjective swallowing difficulties. The mechanisms are not completely understood. Here, we investigated whether remifentanil impairs esophageal motility and hypothesized that this is one possible und
PMID 25923045

Japanese Journal

Naldemedine-induced Opioid Withdrawal Syndrome in a Patient with Breast Cancer without Brain Metastasis: A Case Report

Ishii Koji,Ashizawa Kazuto,Hara Tetsuya,Yamashita Haruna,Yamaguchi Midori,Komatsu Yuya,Ryu Emi,Morishita Satoru,Matsuo Kumi,Kamada Masatsugu,Ikeda Tsunako
Internal Medicine, 2020
… <p>Opioid-induced-constipation (OIC) can be treated by naldemedine and other peripherally acting mu-opioid receptor antagonists (PAMORA) via a novel mechanism. … Her Clinical Opiate-Withdrawal Score (COWS) was 19 (moderate symptoms). …
NAID 130007709027

Role of Neurokinin B and Dynorphin A in pituitary gonadotroph and somatolactotroph cell lines

Mijiddorj Tselmeg,Kanasaki Haruhiko,Purwana Indri N,Oride Aki,Sukhbaatar Unurjargar,Miyazaki Kohji
Endocrine Journal 59(7), 631-640, 2012
… The NKB receptor (NK3R) and the Dyn receptor (the κ-opiate receptor (KOR)) were both detected in LβT2 cells and GH3 cells. …
NAID 130004443814

マウスの移所運動からみたモルヒネ増感現象のオピエート受容体拮抗薬ナロキソンによる時間依存的抑制

栗原久,栗原、久
東京福祉大学・大学院紀要 1(1), 3-10, 2010-05
… Abstract:A significant sensitization to the ambulation-stimulating effect of morphine (10 mg/kg s.c.), a narcotic analgesic drug with agonistic action on opiate receptors, was produced when mice were repeatedly administered morphine at intervals of 3 days, and their ambulation was measured for 3 hr in an activity cage of 20 cm in diameter after each administration. … Naloxone (0.01-1 mg/kg s.c.), an opiate receptor antagonist, blocked the morphine-induced ambulation in a dose-dependent manner. …
NAID 120005397506

Related Pictures

★リンクテーブル★

リンク元	「オピエート受容体」「アヘン受容体」
拡張検索	「μ-opiate receptor」
関連記事	「opiate」「opia」

「オピエート受容体」

　　[★]

英: opiate receptor
同: オピエイト受容体
関: オピオイド受容体、アヘン受容体

「アヘン受容体」

　　[★]

英: opiate receptor
関: オピエート受容体

「μ-opiate receptor」

　　[★] μ-オピエート受容体

「opiate」

　　[★]

n.

オピエート、アヘン剤。(広義)麻酔薬、鎮痛薬。[fig](感覚を)鈍くするもの

adj.

アヘンの、阿片を含む。アヘン剤の、麻酔薬の。催眠/鎮静の。麻酔する

vt.

「opia」

　　[★]

comb form.

視力、視力障害

ex.

diplopia 複視

[pmid8981566-1] Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, Hamon M (December 1996). "International Union of Pharmacology. XII. Classification of opioid receptors" (PDF). Pharmacol. Rev. 48 (4): 567–592. PMID 8981566.

[pmid14754373-2] Janecka A, Fichna J, Janecki T (2004). "Opioid receptors and their ligands". Curr. Top. Med. Chem. 4 (1): 1–17. doi:10.2174/1568026043451618. PMID 14754373.

[pmid15189164-3] Waldhoer M, Bartlett SE, Whistler JL (2004). "Opioid receptors". Annu. Rev. Biochem. 73: 953–990. doi:10.1146/annurev.biochem.73.011303.073940. PMID 15189164.

[pmid4867058-4] Martin, W. R. (December 1967). "Opioid antagonists". Pharmacol. Rev. 19 (4): 463–521. PMID 4867058. Retrieved December 29, 2013.

[5] Ingoglia NA, Dole VP (1970). "Localization of d and l-methadone after intraventricular injection into rat brains.". J. Pharmacol. Exp. Ther. 175 (1): 84–87. PMID 5471456.

[pmid5288759-6] Goldstein A, Lowney LI, Pal BK (August 1971). "Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain". Proc. Natl. Acad. Sci. U.S.A. 68 (8): 1742–7. doi:10.1073/pnas.68.8.1742. PMC 389284. PMID 5288759.

[pmid4687585-7] Pert CB, Snyder SH (March 1973). "Opiate receptor: demonstration in nervous tissue". Science. 179 (4077): 1011–4. doi:10.1126/science.179.4077.1011. PMID 4687585.

[pmid4801733-8] Terenius L (1973). "Stereospecific interaction between narcotic analgesics and a synaptic plasm a membrane fraction of rat cerebral cortex". Acta Pharmacol. Toxicol. (Copenh.). 32 (3): 317–20. doi:10.1111/j.1600-0773.1973.tb01477.x. PMID 4801733.

[pmid4516196-9] Simon EJ, Hiller JM, Edelman I (July 1973). "Stereospecific binding of the potent narcotic analgesic (3H) Etorphine to rat-brain homogenate". Proc. Natl. Acad. Sci. U.S.A. 70 (7): 1947–9. doi:10.1073/pnas.70.7.1947. PMC 433639. PMID 4516196.

[pmid86208-10] Caruso TP; AE Takemori; DL Larson; PS Portoghese (April 1979). "Chloroxymorphamine, an opioid receptor site-directed alkylating agent having narcotic agonist activity". Science. 204 (4390): 316–8. doi:10.1126/science.86208. PMID 86208.

[pmid6259471-11] Caruso TP; DL Larson; PS Portoghese; AE Takemori (December 1980). "Isolation of selective 3H-chlornaltrexamine-bound complexes, possible opioid receptor components in brains of mice". Life Sciences. 27 (22): 2063–9. doi:10.1016/0024-3205(80)90485-3. PMID 6259471.

[pmid16402099-12] Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006). "75 years of opioid research: the exciting but vain quest for the Holy Grail". Br. J. Pharmacol. 147 Suppl 1 (Suppl 1): S153–62. doi:10.1038/sj.bjp.0706435. PMC 1760732. PMID 16402099.

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v t e Opioid receptor modulators

MOR	Agonists (abridged; see here for a full list): 7-Acetoxymitragynine 7-Hydroxymitragynine ψ-Akuammigine α-Chlornaltrexamine α-Narcotine Acetyldihydrocodeine Acetylfentanyl Acrylfentanyl Adrenorphin (metorphamide) AH-7921 Akuammicine Akuammidine Alfentanil Anileridine Apparicine β-Endorphin BAM-12P BAM-18P BAM-22P Benzhydrocodone Benzylmorphine Bezitramide Biphalin BU08070 Buprenorphine Butorphan Butorphanol Butyrfentanyl BW-373U86 Carfentanil Casokefamide Cebranopadol Chloroxymorphamine Codeine DADLE DAMGO (DAGO) Dermorphin Desomorphine Dextromoramide Dextropropoxyphene (propoxyphene) Dezocine Dimenoxadol Dimethylaminopivalophenone Eluxadoline Diamorphine (heroin) Dihydrocodeine Dihydroetorphine Dihydromorphine Diphenoxylate Dipipanone Dynorphin A Embutramide Endomorphin-1 Endomorphin-2 Eseroline Ethylmorphine Etorphine Fentanyl Fluorophen Frakefamide Furanylfentanyl Hemorphin-4 Herkinorin Hodgkinsine Hydrocodone Hydromorphinol Hydromorphone IBNtxA Ketamine Ketobemidone Kratom Laudanosine Lefetamine Leu-enkephalin Levacetylmethadol Levomethorphan Levorphanol Lexanopadol Loperamide Matrine Meptazinol Met-enkephalin (metenkefalin) Methadone Metkefamide Metopon Mitragynine Mitragynine pseudoindoxyl Morphiceptin Morphine Nalbuphine Nalbuphine sebacate NalBzOH Nalmexone Naltalimide Neopine Nicocodeine Nicodicodeine Nicomorphine NKTR-181 Norketamine O-Desmethyltramadol Octreotide Oliceridine OM-3-MNZ Oripavine Oxycodone Oxymorphazone Oxymorphonazine Oxymorphone Oxymorphone phenylhydrazone OxyPNPH Papaver somniferum (opium) Pentazocine Pericine Pethidine (meperidine) Phenazocine Phencyclidine Piminodine Piritramide PL-017 Prodine Propiram PZM21 Racemethorphan Racemorphan Remifentanil Salsolinol Sinomenine Sufentanil Tapentadol Tetrahydropapaveroline TH-030418 Thebaine Thienorphine Tianeptine Tilidine Tramadol Trimebutine TRIMU 5 TRV734 Tubotaiwine U-47700 Valorphin Viminol Xorphanol PAMs: BMS-986121 BMS-986122 Antagonists: (3S,4S)-Picenadol 2-(S)-N,N-(R)-Viminol 4-Caffeoyl-1,5-quinide 4′-Hydroxyflavanone 4',7-Dihydroxyflavone 6β-Naltrexol 6β-Naltrexol-d4 18-MC α-Gliadin β-Chlornaltrexamine β-Funaltrexamine Akuammine Alvimopan AM-251 Apigenin AT-076 Axelopran Bevenopran Catechin Catechin gallate Clocinnamox CTAP CTOP Cyclofoxy Cyprodime Diacetylnalorphine Diprenorphine ECG EGC Epicatechin Eptazocine Gemazocine Ginsenoside R Hyperoside Ibogaine Levallorphan Lobeline LY-255582 LY-2196044 Methocinnamox Methylnaltrexone Methylsamidorphan chloride Naldemedine Nalmefene Nalodeine (N-allylnorcodeine) Nalorphine Nalorphine dinicotinate Naloxazone Naloxegol Naloxol Naloxonazine Naloxone Naltrexazone Naltrexonazine Naltrexone Naltrindole Naringenin Noribogaine Oxilorphan Pawhuskin A Rimonabant Quadazocine Samidorphan Taxifolin Unknown/unsorted: Cannabidiol Coronaridine Cyproterone acetate Dihydroakuuamine Tabernanthine Tetrahydrocannabinol

DOR	Agonists: 6'-GNTI 7-SIOM ADL-5747 (PF-04856881) ADL-5859 Amoxapine AR-M100390 (ARM390) AZD2327 β-Endorphin BAM-18P Biphalin BU-48 Butorphan Butorphanol BW-373U86 Casokefamide Cebranopadol Codeine Cyclazocine DADLE Deltorphin A Deltorphin I Deltorphin II Desmethylclozapine Dezocine Diamorphine (heroin) Dihydroetorphine Dihydromorphine DPDPE DPI-221 DPI-3290 DSLET Ethylketazocine Etorphine Fentanyl FIT Fluorophen Hemorphin-4 Hydrocodone Hydromorphone Ibogaine Isomethadone JNJ-20788560 KNT-127 Kratom Laudanosine Leu-enkephalin Levomethorphan Levorphanol Lexanopadol Lofentanil Met-enkephalin (metenkefalin) Metazocine Metkefamide Mitragynine Mitragynine pseudoindoxyl Morphine N-Phenethyl-14-ethoxymetopon Norbuprenorphine NalBzOH O-Desmethyltramadol Oripavine Oxycodone Oxymorphone Pethidine (meperidine) Proglumide Racemethorphan Racemorphan RWJ-394674 Samidorphan SB-235863 SKF-10047 SNC-80 SNC-162 TAN-67 (SB-205,607) TH-030418 Thebaine Thiobromadol (C-8813) Tianeptine Tonazocine Tramadol TRV250 Xorphanol Zenazocine Antagonists: 4',7-Dihydroxyflavone 5'-NTII 6β-Naltrexol 6β-Naltrexol-d4 α-Santolol β-Chlornaltrexamine Apigenin AT-076 Axelopran Bevenopran BNTX Catechin Catechin gallate Clocinnamox Diacetylnalorphine Diprenorphine ECG EGC Eluxadoline Epicatechin ICI-154129 ICI-174864 LY-255582 LY-2196044 Methylnaltrexone Methylnaltrindole N-Benzylnaltrindole Nalmefene Nalorphine Naltrexone Naltriben Naltrindole Naloxone Naringenin Noribogaine Pawhuskin A Quadazocine SDM25N SoRI-9409 Taxifolin Thienorphine Unknown/unsorted: 18-MC Cannabidiol Coronaridine Cyproterone acetate Tabernanthine Tetrahydrocannabinol

KOR	Agonists: 6'-GNTI 8-CAC 18-MC 14-Methoxymetopon β-Chlornaltrexamine β-Funaltrexamine Adrenorphin (metorphamide) Akuuamicine Alazocine Allomatrine Asimadoline BAM-12P BAM-18P BAM-22P Big dynorphin Bremazocine BRL-52537 Butorphan Butorphanol BW-373U86 Cebranopadol Ciprefadol CR665 Cyclazocine Cyclorphan Cyprenorphine Diamorphine (heroin) Diacetylnalorphine Difelikefalin Dihydroetorphine Dihydromorphine Diprenorphine Dynorphin A Dynorphin B (rimorphin) Eluxadoline Enadoline Eptazocine Erinacine E Ethylketazocine Etorphine Fedotozine Fentanyl Gemazocine GR-89696 GR-103545 Hemorphin-4 Herkinorin HS665 Hydromorphone HZ-2 Ibogaine ICI-199,441 ICI-204,448 Ketamine Ketazocine Laudanosine Leumorphin (dynorphin B-29) Levallorphan Levomethorphan Levorphanol Lexanopadol Lofentanil LPK-26 Lufuradom Matrine MB-1C-OH Menthol Metazocine Metkefamide Mianserin Mirtazapine Morphine Moxazocine MR-2034 N-MPPP Nalbuphine Nalbuphine sebacate NalBzOH Nalfurafine Nalmefene Nalodeine (N-allylnorcodeine) Nalorphine Naltriben Niravoline Norbuprenorphine Norbuprenorphine-3-glucuronide Noribogaine Norketamine O-Desmethyltramadol Oripavine Oxilorphan Oxycodone Pentazocine Pethidine (meperidine) Phenazocine Proxorphan Racemethorphan Racemorphan RB-64 Salvinorin A (salvia) Salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether Samidorphan SKF-10047 Spiradoline (U-62,066) TH-030418 Thienorphine Tifluadom Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline) U-50,488 U-54,494A U-69,593 Xorphanol Antagonists: 4′-Hydroxyflavanone 4',7-Dihydroxyflavone 5'-GNTI 6'-GNTI 6β-Naltrexol 6β-Naltrexol-d4 β-Chlornaltrexamine Buprenorphine/samidorphan Amentoflavone ANTI Apigenin Arodyne AT-076 Axelopran AZ-MTAB Binaltorphimine BU09059 Buprenorphine Catechin Catechin gallate CERC-501 (LY-2456302) Clocinnamox Cyclofoxy Dezocine DIPPA EGC ECG Epicatechin Hyperoside JDTic LY-255582 LY-2196044 LY-2444296 LY-2459989 LY-2795050 MeJDTic Methylnaltrexone ML190 ML350 MR-2266 N-Fluoropropyl-JDTic Naloxone Naltrexone Naltrindole Naringenin Norbinaltorphimine Noribogaine Pawhuskin A PF-4455242 RB-64 Quadazocine Taxifolin UPHIT Zyklophin Unknown/unsorted: Akuammicine Akuammine Coronaridine Cyproterone acetate Dihydroakuuamine Ibogamine Tabernanthine

NOP	Agonists: (Arg14,Lys15)Nociceptin ((pF)Phe⁴)Nociceptin(1-13)NH₂ (Phe¹Ψ(CH₂-NH)Gly²)Nociceptin(1-13)NH₂ Ac-RYYRWK-NH₂ Ac-RYYRIK-NH₂ BU08070 Buprenorphine Cebranopadol Dihydroetorphine Etorphine JNJ-19385899 Levomethorphan Levorphanol Levorphanol Lexanopadol MCOPPB MT-7716 NNC 63-0532 Nociceptin (orphanin FQ) Nociceptin (1-11) Nociceptin (1-13)NH₂ Norbuprenorphine Racemethorphan Racemorphan Ro64-6198 Ro65-6570 SCH-221510 SCH-486757 SR-8993 SR-16435 TH-030418 Antagonists: (Nphe¹)Nociceptin(1-13)NH₂ AT-076 BAN-ORL-24 J-113397 JTC-801 LY-2940094 NalBzOH Nociceptin (1-7) Nocistatin SB-612111 SR-16430 Thienorphine Trap-101 UFP-101

Unsorted	β-Casomorphins Amidorphin BAM-20P Cytochrophin-4 Deprolorphin Gliadorphin (gluteomorphin) Gluten exorphins Hemorphins Kava constituents MEAGL MEAP NEM Neoendorphins Nepetalactone (catnip) Peptide B Peptide E Peptide F Peptide I Rubiscolins Soymorphins

Others	Enkephalinase inhibitors: Amastatin BL-2401 Candoxatril D -Phenylalanine Dexecadotril (retorphan) Ecadotril (sinorphan) Kelatorphan Racecadotril (acetorphan) RB-101 RB-120 RB-3007 Opiorphan Selank Semax Spinorphin Thiorphan Tynorphin Ubenimex (bestatin) Propeptides: β-Lipotropin (proendorphin) Prodynorphin Proenkephalin Pronociceptin Proopiomelanocortin (POMC) Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)

See also: Peptide receptor modulators

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opiate receptor