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Digestive Diseases and Sciences

, Volume 52, Issue 2, pp 502–507 | Cite as

Effect of Naloxone-3-Glucuronide and N-Methylnaloxone on the Motility of the Isolated Rat Colon After Morphine

  • Peter Reber
  • Rudolf Brenneisen
  • Beatrice Flogerzi
  • Catarina Batista
  • Peter Netzer
  • Ulrich Scheurer
Original Paper

Abstract

The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10−4 M, intraluminally) and morphine (10−4 M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrier.

Keywords

Isolated rat colon Morphine Motility inhibition Naloxone-3-glucuronide N-Methylnaloxone Opioid receptor antagonists 

Notes

Acknowledgment

This study was supported by Grant 3200–066693.01 from the Swiss National Science Foundation.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Peter Reber
    • 1
  • Rudolf Brenneisen
    • 2
  • Beatrice Flogerzi
    • 3
  • Catarina Batista
    • 2
  • Peter Netzer
    • 3
  • Ulrich Scheurer
    • 3
  1. 1.Department of Vascular SurgeryLindenhof HospitalBernSwitzerland
  2. 2.Department of Clinical ResearchUniversity of BernBernSwitzerland
  3. 3.Clinic for GastroenterologyUniversity HospitalBernSwitzerland

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