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Inactivity of narcotic glucuronides as analgesics and on guinea-pig ileum.

The effects of morphine, levorphanol, morphine-3-glucuronide and levorphanol-3-glucuronide in the electrically stimulated longitudinal muscle strip of the guinea-pig ileum as well as the analgesic action of intracerebrally injected levorphanol and levorphanol-3-glucuronide in mice have been studied. Morphine-3-glucuronide and levorphanol-3-glucuronide did not influence the tension of the electrically stimulated muscle strip. After hydrolysis, twitch inhibition was the same as with morphine and levorphanol standards. Intracerebral injections of 113 pmol (48.9 ng) of doubly labeled 3H-levorphanol-3-14C-glucuronide produced analgesia in mice. Detailed investigations of the mouse brain have shown 3H radioactivity (levorphanol) not to be bound to glucuronic acid. It was demonstrated that intracerebral injection of comparable small amounts of levorphanol could produce analgesia. These results support the conclusion that analgesia seen after intracerebral injection of levorphanol-3-glucuronide is caused by the free base resulting from hydrolysis in vivo .