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Chiba University Chiba Japan. Mitragyna speciosa KORTH (Rubiaceae) have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids including new natural products. The potent opioid agonistic activities of mitragynine the major constituent of this plant and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines which differ from those of morphine and are responsible for the analgesic activity were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives 7-hydroxymitragynine a minor constituent of M.