Morphine-6-glucuronide is more mu-selective and potent in analgesic tests than morphine.
6-glucuronidation of morphine confers to this widely used analgesic increased potencies both in terms of receptor binding (selectivity) and of antinociceptive properties. In binding studies, 6-glucuronidation of morphine results in increased mu/kappa selectivity (comparable to DAGO). Na+ ions and Gpp(NH)p inhibit similarly the binding of morphine and M6G at the mu sites, suggesting that M6G is a mu agonist. The agonist nature of M6G was further confirmed by its antinociceptive properties: M6G (i.c.v.) was considerably more potent than morphine in the writhing (45 fold) and in the tail-flick (61 fold) tests. Furthermore, M6G induced a longer lasting analgesic effect than morphine. These data strongly suggest that M6G may significantly contribute to the pharmacological activity of morphine.
Francés
B
B
CNRS, Université P. Sabatier, Toulouse, France.
Gout
R
R
Campistron
G
G
Panconi
E
E
Cros
J
J
D000700:Analgesics; D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000378:metabolism / Q000494:pharmacology*; D010147:Pain Measurement; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000700:Analgesics; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C035349:morphine-6-glucuronide; D009020:Morphine