Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa

We have previously elucidated the opiate-like action of mitragynine, an act ive principle isolated from the Thai medicinal plant Mitragyna speciosa. In the present study, effects of the related compound, mitragynine pseudoindo xyl on electrically stimulated contraction in guinea pig ileum and mouse va s deferens, and on its binding affinity in the guinea pig brain membranes w ere studied. Mitragynine pseudoindoxyl inhibited the electrically stimulate d ileum and mouse vas deferens contractions in a concentration-dependent ma nner. In the ileum, the effective concentration is in an nM order, being ne arly equivalent to reported concentrations of the mu-opioid receptor agonis t [D-Ala(2), Met-Phe(4), Gly-ol(5)] enkephalin (DAMGO), and is 100- and 20- fold smaller than those of mitragynine and morphine, respectively. In the v as deferens, it is 35-fold smaller than that of morphine. The inhibitory ac tion of mitragynine pseudoindoxyl in the ileum was antagonized by the non-s elective opioid receptor antagonist naloxone and the mu-receptor antagonist naloxonazine. It was also antagonized by the delta-receptor antagonist nal trindole in the vas deferens. Mitragynine pseudoindoxyl showed a similar bi nding affinity to DAMGO and naltrindole at mu- and delta-receptors, respect ively. However, the affinity at kappa-receptors was negligible. The present study demonstrates that mitragynine pseudoindoxyl a novel alkaloid structu rally different from other opioid agonists, acts on opioid receptors, leadi ng to a potent inhibition of electrically stimulated contraction in the ile um through the mu-receptors and in mouse vas deferens through delta-recepto rs. (C) 1999 Elsevier Science Inc. All rights reserved.