Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/04/10 06:41:46」(JST)

wiki en

Naltrindole is a highly potent, highly selective delta opioid receptor antagonist used in biomedical research. In May 2012 a paper was published in Nature with the structure of naltrindole in complex with the mouse δ-opioid G-protein coupled receptor, solved by X-ray crystallography.^[1]

Drug design

Since peptide compounds are unable to cross the blood–brain barrier, researchers developed naltrindole to be a non-peptide antagonist analog of the delta-preferring endogenous opiate enkephalin. Enkephalin contains an aromatic phenyl group on its Phe⁴ residue, which was hypothesized to be the "address" sequence responsible for the opiate's delta opioid receptor affinity.^[2] Thus, attachment of a phenyl-containing indole molecule to the C-ring of naltrexone's morphinan base successfully produced a drug with the high receptor affinity of naltrexone, but which binds almost exclusively to the delta opioid receptor.^[3]

References

^ Granier, S.; Manglik, A.; Kruse, A. C.; Kobilka, T. S.; Thian, F. S.; Weis, W. I.; Kobilka, B. K. (2012). "Structure of the δ-opioid receptor bound to naltrindole". Nature. 485 (7398): 400–404. doi:10.1038/nature11111. PMC 3523198. PMID 22596164.
^ Lipkowski, AW; Tam, SW; Portoghese, PS (Jul 1986). "Peptides as receptor selectivity modulators of opiate pharmacophores". Journal of Medicinal Chemistry. 29 (7): 1222–5. doi:10.1021/jm00157a018. PMID 2879914.
^ Portoghese, PS; Sultana, M; Takemori, AE (Jan 1988). "Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist". European Journal of Pharmacology. 146 (1): 185–6. doi:10.1016/0014-2999(88)90502-X. PMID 2832195.

English Journal

Remifentanil preconditioning protects the small intestine against ischemia/reperfusion injury via intestinal δ- and μ-opioid receptors.

Shen JT1, Li YS1, Xia ZQ1, Wen SH1, Yao X1, Yang WJ1, Li C1, Liu KX2.
Surgery.Surgery.2016 Feb;159(2):548-59. doi: 10.1016/j.surg.2015.07.028. Epub 2015 Sep 26.
BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury can cause a high rate of mortality in the perioperative period. Remifentanil has been reported to provide protection for organs against I/R injury. We hypothesized that remifentanil preconditioning would attenuate the small intestinal injury i
PMID 26410664

Intrathecal morphine-3-glucuronide-induced nociceptive behavior via Delta-2 opioid receptors in the spinal cord.

Komatsu T1, Katsuyama S2, Nagase H3, Mizoguchi H4, Sakurada C5, Tsuzuki M5, Sakurada S4, Sakurada T6.
Pharmacology, biochemistry, and behavior.Pharmacol Biochem Behav.2016 Jan;140:68-74. doi: 10.1016/j.pbb.2015.10.010. Epub 2015 Oct 22.
Intrathecal (i.t.) injection of morphine-3-glucuronide (M3G), a major metabolite of morphine without analgesic actions, produces severe hindlimb scratching followed by biting and licking in mice. The M3G-induced behavioral response was inhibited dose-dependently by pretreatment with an antisera agai
PMID 26476133

Inhibition of opioid systems in the hypothalamus as well as the mesolimbic area suppresses feeding behavior of mice.

Ikeda H1, Ardianto C2, Yonemochi N2, Yang L2, Ohashi T2, Ikegami M2, Nagase H3, Kamei J2.
Neuroscience.Neuroscience.2015 Dec 17;311:9-21. doi: 10.1016/j.neuroscience.2015.10.002. Epub 2015 Oct 24.
Opioid receptors, especially μ-opioid receptors, in the ventral tegmental area (VTA) and nucleus accumbens (NAcc) are reported to regulate food motivation. However, the roles of μ-, δ- and κ-opioid receptors are not fully understood. Moreover, since μ-, δ- and κ-opioid receptors are reported
PMID 26454026

Japanese Journal

Rewarding Effects of Ethanol Combined with Low Doses of Morphine through Dopamine D1 Receptors

Journal of Nippon Medical School 80(1), 34-41, 2013
NAID 130004147202

Delta-Opioid Receptor Activation Promotes Mesenchymal Stem Cell Survival via PKC/STAT3 Signaling Pathway

Circulation journal : official journal of the Japanese Circulation Society 76(1), 204-212, 2011-12-25
NAID 10030034741

コンビナトリアルケミストリーを活用した天然物とその類縁体の高速合成法の開発

有機合成化学協会誌 : JOURNAL OF Synthetic Organic Chemistry JAPAN 65(8), 795-804, 2007-08-01
NAID 10019753608

「オピオイド」

Naltrindole
Clinical data
Routes of; administration	IV
ATC code	none;
Identifiers
	IUPAC name 17-Cyclopropylmethyl-6,7-dehydro-4,5-epoxy -3,14-dihydroxy-6,7,2',3'-indolomorphinan;
CAS Number	111555-53-4;
PubChem CID	5497186;
IUPHAR/BPS	1641;
ChemSpider	4593753 ;
ChEMBL	CHEMBL567175 ;
Chemical and physical data
Formula	C26H26N2O3
Molar mass	414.496 g/mol
3D model (Jmol)	Interactive image;
	SMILES Oc4c3O[C@H]7c2c(c1ccccc1n2)C[C@@]6(O)[C@H]5N(CC[C@@]67c3c(cc4)C5)CC8CC8 ;
	InChI InChI=1S/C26H26N2O3/c29-19-8-7-15-11-20-26(30)12-17-16-3-1-2-4-18(16)27-22(17)24-25(26,21(15)23(19)31-24)9-10-28(20)13-14-5-6-14/h1-4,7-8,14,20,24,27,29-30H,5-6,9-13H2/t20-,24+,25+,26-/m1/s1 ; Key:WIYUZYBFCWCCQJ-IFKAHUTRSA-N ;
(verify)

　　[★]

英: opioid
同: 類麻薬
関: オピオイド受容体

オピオイド受容体に結合するモルフィン様物質のことを指す。

内因性のオピオイドペプチドが発見され、これらは内因性オピオイドペプチドと呼ばれるようになった。

作用

縮瞳

モルフィンと多くのμ,κアゴニストは瞳孔の縮小を引き起こす。これは瞳孔を支配する副交感神経の興奮による。μアゴニストを中毒量投与すると縮瞳し、pinpoints pupupilsはpathognomonicである。(GOO.559)