Morphine-3-glucuronide: silent regulator of morphine actions

Life Sci. 1994;55(2):149-54. doi: 10.1016/0024-3205(94)90106-6.


To assess whether stoichiometric manipulation of morphine (M) metabolism can enhance analgesia or slow the development of M tolerance we co-administered M-3- glucuronide (M3G) during single or repeated doses of morphine in rats. Although M3G itself lacked analgesic activity, co-injection of M3G with M increased and prolonged analgesia beyond that seen with M. In addition, diminution of the acute analgesic effect of M after 3 once-daily doses of M did not occur after daily co-injection of M3G and M. Thus the traditional view that tolerance to the effects of M is due solely to effects mediated through opioid receptors must be broadened to include the contributions of enzyme induction or stoichiometric equilibration of M3G in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Tolerance
  • Male
  • Morphine / metabolism
  • Morphine / pharmacology*
  • Morphine Derivatives / pharmacology*
  • Nociceptors / drug effects
  • Rats
  • Rats, Sprague-Dawley


  • Morphine Derivatives
  • Morphine
  • morphine-3-glucuronide