Opioid receptor agonist potencies of morphine and morphine-6-glucuronide in the guinea-pig ileum.
It has been suggested that morphine-6-glucuronide, a major metabolite of the opioid analgesic morphine, is more potent as an analgesic than the parent drug. This finding appears not to be due to differences in affinity for opioid receptors. Therefore, in the present study the opioid receptor mediated effects of morphine and morphine-6-glucuronide were compared in vitro using electrically induced contractions of isolated guinea-pig ilea in the absence and presence of increasing concentrations of the selective opioid receptor antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (mu) and norbinaltorphimine (kappa). The results showed a similar efficacy and potency for morphine and morphine-6-glucuronide and indicated that both compounds act reversibly, mainly at mu-opioid receptors. It is concluded that morphine and its metabolite morphine-6-glucuronide are equipotent at mu-opioid receptors.
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
N
N
Schmidt
K
K
Brune
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G
Geisslinger
D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013004:Somatostatin
C529311:CTAP octapeptide; D009022:Morphine Derivatives; D010446:Peptide Fragments; D010455:Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; C035349:morphine-6-glucuronide; D009020:Morphine