Tohoku J. Exp. Med., 1971, 105 (1)

Analgesic Effect of Morphine Glucuronides

KYOICHI SHIMOMURA, OSAMU KAMATA, SHOWA UEKI, SEIU IDA, KAZUTA OGURI, HIDETOSHI YOSHIMURA and HISAO TSUKAMOTO.

Department of Pharmacology, Hygienic and Forensic Chemistry, and Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka

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 27.6 mg/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.

Key words ——morphine; morphine glucuronides; analgesics; morphine tolerance

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Tohoku J. Exp. Med., 1971, 105, 45-52