Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa
by
Matsumoto K, Hatori Y, Murayama T, Tashima K, Wongseripipatana S,
Misawa K, Kitajima M, Takayama H, Horie S.
Laboratory of Pharmacology,
Faculty of Pharmaceutical Sciences,
Josai International University, 1 Gumyo,
Togane, Chiba 283-8555, Japan
Eur J Pharmacol. 2006 Aug 16;


ABSTRACT

7-Hydroxymitragynine, a constituent of the Thai herbal medicine Mitragyna speciosa, has been found to have a potent opioid antinociceptive effect. In the present study, we investigated the mechanism of antinociception and the inhibitory effect on gastrointestinal transit of 7-hydroxymitragynine, and compared its effects with those of morphine. When administered subcutaneously to mice, 7-hydroxymitragynine produced antinociceptive effects about 5.7 and 4.4 times more potent than those of morphine in the tail-flick (ED(50)=0.80 mg/kg) and hot-plate (ED(50)=0.93 mg/kg) tests, respectively. The antinociceptive effect of 7-hydroxymitragynine was significantly blocked by the mu(1)/mu(2)-opioid receptor antagonist beta-funaltrexamine hydrochloride (beta-FNA) and the mu(1)-opioid receptor-selective antagonist naloxonazine in both tests. Thus, 7-hydroxymitragynine acts predominantly on mu-opioid receptors, especially on mu(1)-opioid receptors. Isolated tissue studies further supported its specificity for the mu-opioid receptors. Further, 7-hydroxymintragynine dose-dependently (ED(50)=1.19 mg/kg, s.c.) and significantly inhibited gastrointestinal transit in mice, as morphine does. The inhibitory effect was significantly antagonized by beta-FNA pretreatment, but slightly antagonized by naloxonazine. The ED(50) value of 7-hydroxymitragynine on gastrointestinal transit was larger than its antinociceptive ED(50) value. On the other hand, morphine significantly inhibits gastrointestinal transit at a much smaller dose than its antinociceptive dose. These results suggest that mu-opioid receptor mechanisms mediate the antinociceptive effect and inhibition of gastrointestinal transit. This compound induced more potent antinociceptive effects and was less constipating than morphine.
Mitragynine
7-hydroxymitragynine
The Pleasures of Opium
Opioids and anaesthesia
Mitragyna speciosa (Kratom)
Opium substitute Kratom (Mitragyna speciosa) and mitragynine