Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa

Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine,
an alkaloid from the Thai medicinal herb Mitragyna speciosa

Kenjiro Matsumotoa, Syunji Horiea,Hiromitsu Takayamab, Hayato Ishikawab, Norio Aimib, Dhavadee Pongluxc, Toshihiko Murayamad and Kazuo Watanabed.
Laboratory of Pharmacolgy, Faculty of Pharmaceutical Sciences, Josai International University, Japan
Laboratory of Molecular Structure and Biological Function, Graduate School of Pharmaceutical Sciences, Chiba University, Japan. Faculty of Pharmaceutical Sciences, Chulalongkorn University, Thailand
19 June 2004

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 μ-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 μ-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.