{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:06:39Z","timestamp":1793066799610,"version":"4.5.0"},"reference-count":32,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2014,3]]},"DOI":"10.1124\/jpet.113.208108","type":"journal-article","created":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T04:19:25Z","timestamp":1387340365000},"page":"383-392","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"title":["Orally Active Opioid \u03bc\/\u03b4 Dual Agonist MGM-16, a Derivative of the Indole Alkaloid Mitragynine, Exhibits Potent Antiallodynic Effect on Neuropathic Pain in Mice"],"prefix":"10.1016","volume":"348","author":[{"given":"Kenjiro","family":"Matsumoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Narita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotaka","family":"Muramatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terumi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Misawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Kitajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihito","family":"Tashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi A.","family":"Devi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syunji","family":"Horie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.113.208108_bib1","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.2174\/156802611795371305","article-title":"Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity","volume":"11","author":"Adkins","year":"2011","journal-title":"Curr Top Med Chem"},{"key":"10.1124\/jpet.113.208108_bib2","series-title":"A Dictionary of the Economic Products of the Malay Peninsula,","first-page":"1480","author":"Burkill","year":"1935"},{"key":"10.1124\/jpet.113.208108_bib3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"Chaplan","year":"1994","journal-title":"J Neurosci Methods"},{"key":"10.1124\/jpet.113.208108_bib4","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1016\/0006-2952(73)90196-2","article-title":"Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction","volume":"22","author":"Cheng","year":"1973","journal-title":"Biochem Pharmacol"},{"issue":"Suppl 1","key":"10.1124\/jpet.113.208108_bib5","first-page":"S153","article-title":"75 years of opioid research: the exciting but vain quest for the Holy Grail","volume":"147","author":"Corbett","year":"2006","journal-title":"Br J Pharmacol"},{"key":"10.1124\/jpet.113.208108_bib6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1124\/jpet.112.194308","article-title":"Roles of \u03bc-opioid receptors and nociceptin\/orphanin FQ peptide receptors in buprenorphine-induced physiological responses in primates","volume":"343","author":"Cremeans","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.113.208108_bib7","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.pain.2010.06.019","article-title":"The evidence for pharmacological treatment of neuropathic pain","volume":"150","author":"Finnerup","year":"2010","journal-title":"Pain"},{"key":"10.1124\/jpet.113.208108_bib8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1055\/s-2005-837822","article-title":"Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum","volume":"71","author":"Horie","year":"2005","journal-title":"Planta Med"},{"key":"10.1124\/jpet.113.208108_bib9","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.pain.2010.12.031","article-title":"Genetic ablation of delta opioid receptors in nociceptive sensory neurons increases chronic pain and abolishes opioid analgesia","volume":"152","author":"Gaveriaux-Ruff","year":"2011","journal-title":"Pain"},{"key":"10.1124\/jpet.113.208108_bib10","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1097\/ACO.0b013e3282effaa7","article-title":"Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions","volume":"20","author":"Gilron","year":"2007","journal-title":"Curr Opin Anaesthesiol"},{"key":"10.1124\/jpet.113.208108_bib11","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1056\/NEJMoa042580","article-title":"Morphine, gabapentin, or their combination for neuropathic pain","volume":"352","author":"Gilron","year":"2005","journal-title":"N Engl J Med"},{"key":"10.1124\/jpet.113.208108_bib12","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.pain.2006.08.003","article-title":"Anti-allodynic effects of peripheral delta opioid receptors in neuropathic pain","volume":"127","author":"Kabli","year":"2007","journal-title":"Pain"},{"key":"10.1124\/jpet.113.208108_bib13","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.neuroscience.2008.02.031","article-title":"Pharmacological characterization and gene expression profiling of an L5\/L6 spinal nerve ligation model for neuropathic pain in mice","volume":"153","author":"Kiso","year":"2008","journal-title":"Neuroscience"},{"key":"10.1124\/jpet.113.208108_bib14","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0022-3565(25)03549-9","article-title":"A simplified method of evaluating dose-effect experiments","volume":"96","author":"Litchfield","year":"1949","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.113.208108_bib15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0304-3959(98)00045-1","article-title":"Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates","volume":"76","author":"Malmberg","year":"1998","journal-title":"Pain"},{"key":"10.1124\/jpet.113.208108_bib16","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1097\/00000542-200404000-00022","article-title":"Nerve injury induces a tonic bilateral mu-opioid receptor-mediated inhibitory effect on mechanical allodynia in mice","volume":"100","author":"Mansikka","year":"2004","journal-title":"Anesthesiology"},{"key":"10.1124\/jpet.113.208108_bib17","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejphar.2006.08.013","article-title":"Involvement of \u03bc-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa","volume":"549","author":"Matsumoto","year":"2006","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/jpet.113.208108_bib18","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1016\/j.lfs.2003.09.054","article-title":"Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa","volume":"74","author":"Matsumoto","year":"2004","journal-title":"Life Sci"},{"key":"10.1124\/jpet.113.208108_bib19","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.lfs.2004.10.086","article-title":"Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa","volume":"78","author":"Matsumoto","year":"2005","journal-title":"Life Sci"},{"key":"10.1124\/jpet.113.208108_bib20","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1016\/j.lfs.2005.09.030","article-title":"Partial agonistic effect of 9-hydroxycorynantheidine on mu-opioid receptor in the guinea-pig ileum","volume":"78","author":"Matsumoto","year":"2006","journal-title":"Life Sci"},{"key":"10.1124\/jpet.113.208108_bib21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.neuropharm.2008.05.003","volume":"55","author":"Matsumoto","year":"2008","journal-title":"Neuropharmacology"},{"key":"10.1124\/jpet.113.208108_bib22","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.lfs.2005.04.042","article-title":"Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens","volume":"78","author":"Matsumoto","year":"2005","journal-title":"Life Sci"},{"key":"10.1124\/jpet.113.208108_bib23","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1111\/j.1460-9568.2006.04569.x","article-title":"Neuropathic pain is enhanced in delta-opioid receptor knockout mice","volume":"23","author":"Nadal","year":"2006","journal-title":"Eur J Neurosci"},{"key":"10.1124\/jpet.113.208108_bib24","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/sj.npp.1301471","article-title":"Comparative pharmacological profiles of morphine and oxycodone under a neuropathic pain-like state in mice: evidence for less sensitivity to morphine","volume":"33","author":"Narita","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.113.208108_bib25","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1124\/jpet.111.188987","article-title":"\u03b4-Opioid mechanisms for ADL5747 and ADL5859 effects in mice: analgesia, locomotion, and receptor internalization","volume":"342","author":"Nozaki","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.113.208108_bib26","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1021\/jm400143z","article-title":"Orally active opioid compounds from a non-poppy source","volume":"56","author":"Raffa","year":"2013","journal-title":"J Med Chem"},{"key":"10.1124\/jpet.113.208108_bib28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0304-3959(90)91074-S","article-title":"A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury","volume":"43","author":"Seltzer","year":"1990","journal-title":"Pain"},{"key":"10.1124\/jpet.113.208108_bib29","first-page":"21","article-title":"A study of kratom eaters in Thailand","volume":"27","author":"Suwanlert","year":"1975","journal-title":"Bull Narc"},{"key":"10.1124\/jpet.113.208108_bib30","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1248\/cpb.52.916","article-title":"Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa","volume":"52","author":"Takayama","year":"2004","journal-title":"Chem Pharm Bull (Tokyo)"},{"key":"10.1124\/jpet.113.208108_bib31","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1021\/jm010576e","article-title":"Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands","volume":"45","author":"Takayama","year":"2002","journal-title":"J Med Chem"},{"key":"10.1124\/jpet.113.208108_bib32","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.1021\/ol062173k","article-title":"New procedure to mask the 2,3-\u03c0 bond of the indole nucleus and its application to the preparation of potent opioid receptor agonists with a Corynanthe skeleton","volume":"8","author":"Takayama","year":"2006","journal-title":"Org Lett"},{"key":"10.1124\/jpet.113.208108_bib33","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0024-3205(97)00023-4","article-title":"Inhibitory effect of mitragynine, an alkaloid with analgesic effect from Thai medicinal plant Mitragyna speciosa, on electrically stimulated contraction of isolated guinea-pig ileum through the opioid receptor","volume":"60","author":"Watanabe","year":"1997","journal-title":"Life Sci"}],"updated-by":[{"DOI":"10.1124\/jpet.112.208108err","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000}}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524272232?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524272232?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.113.208108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T20:10:21Z","timestamp":1739995821000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524272232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["S0022356524272232"],"URL":"https:\/\/doi.org\/10.1124\/jpet.113.208108","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2014,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Orally Active Opioid \u03bc\/\u03b4 Dual Agonist MGM-16, a Derivative of the Indole Alkaloid Mitragynine, Exhibits Potent Antiallodynic Effect on Neuropathic Pain in Mice","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.113.208108","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2014 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}