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.
Lipkowski
A W
AW
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Carr
D B
DB
Langlade
A
A
Osgood
P F
PF
Szyfelbein
S K
SK
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