Pharmacological action of mitragynine

Abstract

Pharmalogical action of mitragynine, an indole alkaloid from the leaves of Mitragyna speciosa (Korth.) was studied and reported in this dissertation. In mice, it was found that mitragynine, 30 mg/kg, produced significant antinociceptive effect using hot plate test, writhing test and formalin test in a dose dependent manner. In contrast to morphine, this antinociceptive effect was not antagonized by naloxone, an opiate antagonist. Mitragynine increased locomotor activity in mice, suggesting that it was a central nervous system stimulant. The increased locomotor activity was antagonized by haloperidol, a dopamine antagonist. However, mitragynine did not show any dopamine agonist, antagonist or dopamine releasing agent when tested by rotational behavior and dopamine-2 receptor binding assay. Mitragynine, at the dose of 15 and 30 mg/kg body weight, also did not affect the dopamine or serotonin level in striatum in microdialysis study. Head twitch but not head weaving induced by 5-Methoxy-N,N-dimethyl tryptamine was blocked by mitragynine. Mitragynine had no direct effect on firing rate of Purkinje cell in cerebellum, nor did it alter the effects of GABA and serotonin on Purkinje cell. Mitragynine significantly decresed body temperature. From the results, mechanism of action of mitragynine is proposed as an antagonist on serotonin-2 (5-HT2) receptor or α-2 adrenoceptor.