Analgesic Effect of Morphine Glucuronides

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Abstract
Pharmacological properties of morphine-3-glucuronide and morphine-6-glucuronide were studied in mice and compared with those of morphine. 1) The analgesic effect of morphine-6-glucuronide was 3 to 4 times as potent and approximately 2 times as long in duration as that of morphine when injected subcutaneously. Morphine-3-glucuronide, however, showed no analgesic effect even in a dose of 27.6mg/kg. 2) The analgesic effect of morphine-6-glucuronide was about 45 times as potent as that of morphine, when injected intracerebrally in mice, but morphine-3-glucuronide had no effect. 3) After intraperitoneal injection of morphine-6-glucuronide in rats, only conjugated morphine was detected in the brain by chromatographic examination but not free morphine. 4) Morphine-6-glucuronide was also antagonized by nalorphine though to slightly lesser degree than morphine. 5) Development of tolerance to morphine-6-glucuronide in analgesic effect was almost the same in degree as that to morphine. Cross tolerance between morphine-6-glucuronide and morphine was observed as well.

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