Thienorphine

{{Short description|Chemical compound}}

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| IUPAC_name = (1R,2R,6S,15R)-3-(cyclopropylmethyl)-16-[(2R)-2-hydroxy-4-(thiophen-2-yl)butan-2-yl]-15-methoxy-13-oxa-3-azahexacyclo[13.2.2.1^2,8.0^1,6.0^6,14.0^7,12]icosa-7,9,11-trien-11-ol

| image = Thienorphine.svg

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| PubChem = 102212421

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| ChemSpiderID = 58539334

| C=31 | H=39 | N=1 | O=4 | S=1

| smiles = C[C@@](CCc1cccs1)([C@H]2C[C@@]34CCC2([C@H]5[C@@]36CCN([C@@H]4Cc7c6c(c(cc7)O)O5)CC8CC8)OC)O

| StdInChI = 1S/C31H39NO4S/c1-28(34,10-9-21-4-3-15-37-21)23-17-29-11-12-31(23,35-2)27-30(29)13-14-32(18-19-5-6-19)24(29)16-20-7-8-22(33)26(36-27)25(20)30/h3-4,7-8,15,19,23-24,27,33-34H,5-6,9-14,16-18H2,1-2H3/t23-,24-,27-,28-,29-,30+,31-/m1/s1

| StdInChIKey = WTGSHWLSWVFVAH-JTTXIWGLSA-N

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Thienorphine is a very potent, extremely long-acting, orally-active opioid analgesic with mixed agonist–antagonist properties which was developed by the Beijing Institute of Pharmacology and Toxicology as a potential treatment for opioid dependence.{{cite journal | vauthors = Liu H, Zhong BH, Liu CH, Wu B, Gong ZH | url=http://acta-arhiv.chem-soc.si/52/52-1-80.pdf | title= Synthesis, Crystal Structural and Pharmacological Study of N-Cyclopropylmehtyl-7α-[(R)-1-hydroxyl-1-methyl-3-(thien-2-yl)propyl]-6,14-endoethanotetrahydronooripavine | journal=Acta Chimica Slovenica | year=2005 | volume=52 | issue=1 | pages=80–85 | issn=1318-0207}}{{cite journal | vauthors = Yu G, Liu YS, Yan LD, Wen Q, Gong ZH | title = [Structure-activity relationships analysis of thienorphine and its derivatives] | language = zh | journal = Yao Xue Xue Bao | trans-journal = Acta Pharmaceutica Sinica | volume = 44 | issue = 7 | pages = 726–730 | date = July 2009 | pmid = 19806910 }}{{cite journal | vauthors = Yu G, Li SH, Cui MX, Yan LD, Yong Z, Zhou PL, Su RB, Gong ZH | display-authors = 6 | title = Multiple mechanisms underlying the long duration of action of thienorphine, a novel partial opioid agonist for the treatment of addiction | journal = CNS Neuroscience & Therapeutics | volume = 20 | issue = 3 | pages = 282–288 | date = March 2014 | pmid = 24330593 | pmc = 6492997 | doi = 10.1111/cns.12210 }} It is a high-affinity, balanced ligand of the μ- (K_i = 0.22 nM), δ- (K_i = 0.69 nM), and κ-opioid receptors (K_i = 0.14 nM), behaving as a partial agonist of the μ- (E_max = 19%–28%) and κ-opioid receptors (E_max = 65–75%) and as an antagonist of the δ-opioid receptor.{{cite journal | vauthors = Yu G, Yue YJ, Cui MX, Gong ZH | title = Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 318 | issue = 1 | pages = 282–287 | date = July 2006 | pmid = 16569757 | doi = 10.1124/jpet.105.099937 | s2cid = 24549788 }}{{cite journal | vauthors = Li JX, Becker GL, Traynor JR, Gong ZH, France CP | title = Thienorphine: receptor binding and behavioral effects in rhesus monkeys | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 321 | issue = 1 | pages = 227–236 | date = April 2007 | pmid = 17220427 | doi = 10.1124/jpet.106.113290 | s2cid = 11477535 }}{{cite journal | vauthors = Wen Q, Yu G, Li YL, Yan LD, Gong ZH | title = Pharmacological mechanisms underlying the antinociceptive and tolerance effects of the 6,14-bridged oripavine compound 030418 | journal = Acta Pharmacologica Sinica | volume = 32 | issue = 10 | pages = 1215–1224 | date = October 2011 | pmid = 21863064 | pmc = 4010084 | doi = 10.1038/aps.2011.83 }} It also possesses relatively low affinity for the nociceptin receptor (K_i = 36.5 nM), where it acts as an antagonist.