Morphine-3-glucuronide: silent regulator of morphine actions.
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.
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
A W
AW
Lipkowski
D B
DB
Carr
A
A
Langlade
P F
PF
Osgood
S K
SK
Szyfelbein
D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009022:Morphine Derivatives; D009020:Morphine; C018108:morphine-3-glucuronide