RESUMO
We have previously elucidated the opiate-like action of mitragynine, an active principle isolated from the Thai medicinal plant Mitragyna speciosa. In the present study, effects of the related compound, mitragynine pseudoindoxyl on electrically stimulated contraction in guinea pig ileum and mouse vas deferens, and on its binding affinity in the guinea pig brain membranes were studied. Mitragynine pseudoindoxyl inhibited the electrically stimulated ileum and mouse vas deferens contractions in a concentration-dependent manner. In the ileum, the effective concentration is in an nM order, being nearly equivalent to reported concentrations of the micro-opioid receptor agonist [D-Ala2, Met-Phe4, Gly-ol5] enkephalin (DAMGO), and is 100- and 20-fold smaller than those of mitragynine and morphine, respectively. In the vas deferens, it is 35-fold smaller than that of morphine. The inhibitory action of mitragynine pseudoindoxyl in the ileum was antagonized by the non-selective opioid receptor antagonist naloxone and the micro-receptor antagonist naloxonazine. It was also antagonized by the delta-receptor antagonist naltrindole in the vas deferens. Mitragynine pseudoindoxyl showed a similar binding affinity to DAMGO and naltrindole at micro- and delta-receptors, respectively. However, the affinity at kappa-receptors was negligible. The present study demonstrates that mitragynine pseudoindoxyl, a novel alkaloid structurally different from other opioid agonists, acts on opioid receptors, leading to a potent inhibition of electrically stimulated contraction in the ileum through the micro-receptors and in mouse vas deferens through delta-receptors.
Assuntos
Analgésicos/farmacologia , Plantas Medicinais/química , Receptores Opioides/agonistas , Alcaloides de Triptamina e Secologanina/farmacologia , Animais , Ligação Competitiva , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Estimulação Elétrica , Cobaias , Íleo/efeitos dos fármacos , Íleo/fisiologia , Técnicas In Vitro , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/inervação , Músculo Liso/fisiologia , Naloxona/análogos & derivados , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Receptores Opioides/metabolismo , Tailândia , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/fisiologiaRESUMO
A novel glycosidic alkaloid, hunterioside, together with strictosidinic acid was isolated from Hunteria zeylanica, and the structure was found to be 6'-alpha-D-glucoside of strictosidinic acid. This isolation is the first finding of a bioside congener of monoterpenoid indole alkaloid glucosides.
