Inhibitory effect of mitragynine, an alkaloid with analgesic effect from Thai medicinal plant Mitragyna speciosa, on electrically stimulated contraction of isolated guinea-pig ileum through the opioid receptor

Effect of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna speciosa), on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 nM - 3 mu M) inhibited the ileum contraction elicited by electrical stimulation, and its pD(2) value was 6.91 +/- 0.04 (n = 5). Morphine (1 nM - 1 mu M) also inhibited the electrically stimulated contraction in a concentration-dependent manner (pD(2) 7.68 +/- 0.11; n = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3 - 10 mu M) did not show any effect on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10 - 300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of concentration-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA(2)) in the presence of mitragynine or morphine. Mitragynine (3 - 10 mu M) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 mu M) and atropine (1 mu M) inhibited the withdrawal contraction. The present results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor.