title: Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa.
abstract: 7-Hydroxymitragynine is a potent opioid analgesic alkaloid isolated from the Thai medicinal herb Mitragyna speciosa. In the present study, we investigated the opioid receptor subtype responsible for the analgesic effect of this compound. In addition, we tested whether development of tolerance, cross-tolerance to morphine and naloxone-induced withdrawal signs were observed in chronically 7-hydroxymitragynine-treated mice. Subcutaneous (s.c.) administration of 7-hydroxymitragynine produced a potent antinociceptive effect mainly through activation of mu-opioid receptors. Tolerance to the antinociceptive effect of 7-hydroxymitragynine developed as occurs to morphine. Cross-tolerance to morphine was evident in mice rendered tolerant to 7-hydroxymitragynine and vice versa. Naloxone-induced withdrawal signs were elicited equally in mice chronically treated with 7-hydroxymitragynine or morphine. 7-Hydroxymitragynine exhibited a potent antinociceptive effect based on activation of mu-opioid receptors and its morphine-like pharmacological character, but 7-hydroxymitragynine is structurally different from morphine. These interesting characters of 7-hydroxymitragynine promote further investigation of it as a novel lead compound for opioid studies.
authors.affiliation: Laboratory of Pharmacolgy, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Syunji
authors.initials: S
authors.lastname: Horie
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takayama
authors.forename: Hayato
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Aimi
authors.forename: Dhavadee
authors.initials: D
authors.lastname: Ponglux
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000700:Analgesics; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D032065:Mitragyna / Q000009:adverse effects* / Q000737:chemistry*; D008958:Models, Molecular; D009019:Morphinans / Q000494:pharmacology; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D046948:Secologanin Tryptamine Alkaloids / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013785:Thailand
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D046948:Secologanin Tryptamine Alkaloids; C058450:cyprodime; C482678:7-hydroxymitragynine; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole