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Planta Med 2005; 71(3): 231-236
DOI: 10.1055/s-2005-837822
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Indole Alkaloids of a Thai Medicinal Herb, Mitragyna speciosa, that has Opioid Agonistic Effect in Guinea-Pig Ileum

Syunji Horie1 , Fumi Koyama1 , Hiromitsu Takayama2 , Hayato Ishikawa2 , Norio Aimi2 , Dhavadee Ponglux3 , Kenjiro Matsumoto1 , Toshihiko Murayama1
  • 1Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
  • 2Laboratory of Molecular Structure and Biological Function, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
  • 3Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
Weitere Informationen

Publikationsverlauf

Received: June 15, 2004

Accepted: September 5, 2004

Publikationsdatum:
15. März 2005 (online)

    Lizenzen und Reprints

Abstract

Recently, we found that mitragynine, a major constituent of Mitragyna speciosa, has an opioid agonistic activity, but its weak potency could not explain the opium-like effect of this plant. In the present study, bioassay-guided fractionation of the crude extract of the leaves of M. speciosa was carried out to search for potent opioid agonists other than mitragynine. Opioid agonistic activities were evaluated using twitch contraction induced by electrical stimulation in guinea-pig ileum. The crude extract of M. speciosa inhibited the twitch contraction in a concentration-dependent manner. The inhibition was reversed by naloxone. The opioid effect was detected only in the crude base fraction, which was followed by the isolation of five indole alkaloids. Among these alkaloids, 7-hydroxymitragynine showed the most potent opioid effect on the electrically-stimulated contraction (pD2 = 8.38 ± 0.12). The potency, calculated using pD2 values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively. Antagonism of naloxone on concentration-response curves for 7-hydroxymitragynine confirmed its opioid effect. These results suggest that the opioid effect of M. speciosa is mostly based on the activity of 7-hydroxymitragynine.

Key words

Mitragyna speciosa - Rubiaceae - morphine - ileum - opioid receptor - mitragynine - nociceptin - opioid receptor-like 1 receptor

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Syunji Horie, Ph. D.

Laboratory of Chemical Pharmacology

Graduate School of Pharmaceutical Sciences

Chiba University

1-8-1 Inohana

Chuo-ku

Chiba 260-8675

Japan

Telefon: +81-43-226-2875

Fax: +81-43-226-2875

eMail: syunji@p.chiba-u.ac.jp

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