Honors Theses

Date of Award

2008

Document Type

Undergraduate Thesis

Department

Chemistry and Biochemistry

First Advisor

Abir El-Alfy

Relational Format

Dissertation/Thesis

Abstract

Mitragynine is a major alkaloid extracted from the leaves of the Thai traditional herb, Mitrcigymi speciosa Korth (Rubiaceae). The extracts of this plant have been used as substitutes for opium and recent studies have reported that mitragynine possesses antinociceptive actions mediated via the mu opioid receptors. Nonetheless, structural features of mitragynine do not fit the classical opiate ligands. Thus the primary objectives of this study were to evaluate the antinociceptive effect of mitragynine and its synthetic analogs to determine the molecular basis of mitragynine binding to opioid receptors in order to provide better understanding of the potential therapeutic roles of these compounds. The antinociceptive effect of intraperitoneal (i.p.) injection of mitragynine (10-30 mg/kg) was investigated as compared to morphine (5-20 mg/kg) using the tailflick and hotplate tests. In both tests, mitragynine exerted a dose-dependent antinociceptive activity that was maximal at 30 min but was less potent than morphine. Such effects were completely abolished by pretreatment with the opioid receptor antagonist naloxone (10 mg/kg, i.p.). The synthetic mitragynine analogs MC 183, MCI86, and MC 187 exhibited no antinociceptive activity at 30 mg/kg dose (i.p.) in either the hotplate or tailflick tests. The present study will provide better insight into the mechanism of action of mitragynine as well as the pharmacology of opioid receptors. Such understanding may lead to the generation of a new class of analgesics of potential therapeutic value.

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