Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa

Life Sci. 2004 Mar 12;74(17):2143-55. doi: 10.1016/j.lfs.2003.09.054.

Abstract

Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study, we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding assays revealed that 7-hydroxymitragynine has a higher affinity for micro-opioid receptors relative to the other opioid receptors. Administration of 7-hydroxymitragynine (2.5-10 mg/kg, s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in both tests. When orally administered, 7-hydroxymitragynine (5-10 mg/kg) showed potent antinociceptive activities in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / physiology
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mitragyna* / chemistry
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Pain / drug therapy*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Receptors, Opioid, mu / metabolism
  • Secologanin Tryptamine Alkaloids / administration & dosage
  • Secologanin Tryptamine Alkaloids / metabolism
  • Secologanin Tryptamine Alkaloids / pharmacology*
  • Tail

Substances

  • Analgesics, Opioid
  • Plant Extracts
  • Receptors, Opioid, mu
  • Secologanin Tryptamine Alkaloids
  • 7-hydroxymitragynine
  • mitragynine