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Morphine-3-Glucuronide — A potent antagonist of morphine analgesia

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Page 1: Morphine-3-Glucuronide — A potent antagonist of morphine analgesia

S186

---- -_-a_ -_ ------ Poster 59 : BROWN Mon-Tues ; ACC Hall E

Abs No 366 and 3Khaled El"----'---

Medici

Opiate Analgesia - Pharmacology I

MORPHINE-3-GLUCURONIDE - A POTENT ANTAGONIST OF MORPHINE ANALGESIA. Poster 60 Maree T. Smith*and Tess Cramond, Division of Anaesthetics, Department BROWN Mon-Tues of Surgery, University of Queensland, Block 6, Royal Brisbane Hospital, ACC Hall E Brisbane, Australia. 4029. Abs No 367

AIM OF INVESTIGATION: This study was designed to test the I

hypothesis that "Morphine-3-qlucuronide, the ma.ior plasma and urinary metabolite of morphine, could antagonize the analgesic effects of‘morphine and/or Morphine-6- glucuronide". METHODS: Morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and morphine were

ad-red alone and in combination to male Sprague-Dawley derived rats by the intracerebroventricular (i.c.v.) and the intra-peritoneal (i.p.) routes. The Degree of Analgesia developed was quantitated using the Rat Tail Flick Test.

RESULTS: M3G, administered by the i.c.v. route, (i) is a potent dose-dependent an-t to the analgesic effects of subsequently administered i,c.v. morphine (ii) antagonizes the analgesia of subsequently administered i.c.v. M6G. In addition, i.p. M3G antagonizes the analgesic effects of subsequently administered i.p. morphine. The 'morphine-withdrawal' effects observed after i.c.v. M3G administration (allodynia, itch, tremor, whole body shakes and seizures), are reversible in a dose-dependent manner, by the subsequent administration of i.c.v. morphine.

CONCLUSION: The major plasma and urinary metabolite of morphine, M3G, antagonizes the analgesic effects of morphine and its analgesic metabolite, M6G. This would tend to suggest that morphine-3-glucuronide has a major role to play in the development of morphine tolerance.