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

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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.

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Acknowledgment

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

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Authors and Affiliations

  1. Department of Vascular Surgery, Lindenhof Hospital, Bern, Switzerland

    Peter Reber

  2. Department of Clinical Research, University of Bern, Murtenstrasse 35, CH-3010, Bern, Switzerland

    Rudolf Brenneisen & Catarina Batista

  3. Clinic for Gastroenterology, University Hospital, Bern, Switzerland

    Beatrice Flogerzi, Peter Netzer & Ulrich Scheurer

Authors
  1. Peter Reber
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  2. Rudolf Brenneisen
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  3. Beatrice Flogerzi
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  4. Catarina Batista
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  5. Peter Netzer
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  6. Ulrich Scheurer
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Correspondence to Rudolf Brenneisen.

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Reber, P., Brenneisen, R., Flogerzi, B. et al. Effect of Naloxone-3-Glucuronide and N-Methylnaloxone on the Motility of the Isolated Rat Colon After Morphine. Dig Dis Sci 52, 502–507 (2007). https://doi.org/10.1007/s10620-006-9563-9

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  • DOI: https://doi.org/10.1007/s10620-006-9563-9

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