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Equine veterinary journal2005; 37(4); 325-328; doi: 10.2746/0425164054529346

In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure.

Abstract: Although potent analgesics, opioids decrease intestinal activity, leading to ileus in many species. N-methylnaltrexone (MNTX), an opioid antagonist which does not cross the blood-brain barrier and antagonises the morphine effect on the intestine, directly stimulates motility and restores function without affecting analgesic properties. While its use has been reported in human subjects, there is no information with regard to its usage in the horse. Objective: To determine whether MNTX has an effect on contractile activity of the equine jejunum and pelvic flexure. Methods: Using circular smooth muscle strips obtained from 8 mature horses, increasing concentrations of MNTX were added to tissue baths in the range of 1 x 10(-9) to 1 x 10(-5) mol/l, and contractile responses were recorded for 3 mins. Data were analysed using a repeated measures ANOVA to determine whether there was a significant drug effect compared to baseline activity. Data were analysed between the jejunum and pelvic flexure using a Mann-Whitney U test. Statistical significance was established as P < 0.05. Results: The administration of MNTX significantly increased the contractile frequency and amplitude at all concentrations relative to baseline (P < 0.0001) for the jejunum. The response was greatest at 1 x 10(-7) mol/l (P = 0.0005), with a mean difference from baseline of 115.12 g/cm2. The highest concentration evaluated (1 x 10(-5) mol/l) had a mean contractile strength of 69.76 g/cm2, which was significantly greater than baseline activity (P = 0.04). A significant increase in contractile activity for the colon was detected at 3 x 10(-7) mol/l and all subsequent concentrations (P < 0.04). Unlike the jejunum, the contractile activity of the pelvic flexure increased progressively with the addition of each subsequent concentration. Conclusions: N-methylnaltrexone has a direct effect on circular smooth muscle of the equine jejunum and pelvic flexure resulting in an increase in contractile activity. Conclusions: N-methylnaltrexone could potentially be used in conjunction with morphine to provide potent and effective analgesia without compromising intestinal function. Further in vivo investigations are required to determine whether this agent antagonises morphine's effect on motility.
Publication Date: 2005-07-21 PubMed ID: 16028621DOI: 10.2746/0425164054529346Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores the effects of N-methylnaltrexone (MNTX) on the motility of the equine jejunum and pelvic flexure. The study suggests MNTX could potentially be used in conjunction with morphine to offer potent analgesia without affecting intestinal function in horses.

Objective and Methods

In this research, the authors aimed to perceive how MNTX impacts the contractile activity of the equine jejunum and pelvic flexure. MNTX is an opioid antagonist used to combat the morphine effect on the intestine, which decreases intestinal activity while retaining morphine’s analgesic properties. These studies had been undertaken on humans before, but this was the first time the effects of MNTX were studied in horses.

  • The experimental procedure involved obtaining circular smooth muscle strips from 8 mature horses.
  • These strips were placed in tissue baths with increased MNTX concentrations, ranging from 1 x 10(-9) to 1 x 10(-5) mol/l, and contractile responses were recorded for 3 mins.
  • The collected data was then analyzed using a repeated measures ANOVA to discern any significant drug effect contrasted with the baseline activity. Comparative analysis was also executed between the jejunum and the pelvic flexure using a Mann-Whitney U test.

Results

The results indicated that MNTX injections significantly powered up the contractile frequency and amplitude for the jejunum at all concentration levels tested, when compared to baseline actvity.

  • Maximum response was noted at 1 x 10(-7) mol/l, with a significant increase from the baseline of 115.12 g/cm2.
  • The highest concentration evaluated (1 x 10(-5) mol/l) recorded a mean contractile strength of 69.76 g/cm2, which was significantly greater than the baseline activity.
  • Significant increase in contractile activity for the colon was observed at 3 x 10(-7) mol/l and at all higher concentrations.
  • Unlike the jejunum, pelvic flexure’s contractile activity increased consistently with the sequential addition of each concentration.

Conclusion

The results evidence that MNTX directly influences the circular smooth muscle of the equine jejunum and the pelvic flexure leading to a surge in contractile activity. This suggests the possible use of MNTX together with morphine to provide effective pain relief without disrupting intestinal function in horses. However, the authors note that further in vivo investigations are necessary to assert whether MNTX counters morphine’s impact on motility. These findings lay promising groundwork for potential developments in equine pain management.

Cite This Article

APA
van Hoogmoed LM, Boscan PL. (2005). In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure. Equine Vet J, 37(4), 325-328. https://doi.org/10.2746/0425164054529346

Publication

ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 37
Issue: 4
Pages: 325-328

Researcher Affiliations

van Hoogmoed, L M
  • Comparative Gastroenterology Laboratory, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Boscan, P L

    MeSH Terms

    • Analysis of Variance
    • Animals
    • Dose-Response Relationship, Drug
    • Gastrointestinal Motility / drug effects
    • Horses / physiology
    • Jejunum / drug effects
    • Jejunum / physiology
    • Muscle Contraction / drug effects
    • Muscle, Smooth / drug effects
    • Muscle, Smooth / physiology
    • Naltrexone / analogs & derivatives
    • Naltrexone / pharmacology
    • Narcotic Antagonists / pharmacology
    • Pelvis
    • Quaternary Ammonium Compounds
    • Tissue Culture Techniques / veterinary

    Citations

    This article has been cited 2 times.
    1. Greenwood-Van Meerveld B, Standifer KM. Methylnaltrexone in the treatment of opioid-induced constipation. Clin Exp Gastroenterol 2008;1:49-58.
      doi: 10.2147/ceg.s3889pubmed: 21677823google scholar: lookup
    2. Garnock-Jones KP, McKeage K. Methylnaltrexone. Drugs 2010 May 7;70(7):919-28.