Dose‐Related Antagonism of the Emetic Effect of Morphine by Methylnaltrexone in Dogs

@article{Foss1993DoseRelatedAO,
  title={Dose‐Related Antagonism of the Emetic Effect of Morphine by Methylnaltrexone in Dogs},
  author={Joseph F. Foss and Alan S. Bass and Leon I. Goldberg},
  journal={The Journal of Clinical Pharmacology},
  year={1993},
  volume={33}
}
Opioids administered to produce analgesia cause unwanted emesis in patients (incidence 20%–30%, depending on situation). Tests in animals show that quaternary narcotic antagonists like methylnaltrexone (MNTX) do not affect the analgesic potency of morphine, but such compounds have not been examined for their potential to antagonize morphine‐induced emesis. To determine the effects of MNTX on emetic response, we assigned 85 dogs to one of 11 groups challenged with morphine alone or morphine and… 

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Findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated are consistent with findings that cannabinoid receptor agonists will prevent opioid-induced vomiting.

Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial.

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The potential for μ‐opioid receptor agonists to be anti‐emetic in humans: a review of clinical data

  • K. D. Johnston
  • Biology, Medicine
    Acta anaesthesiologica Scandinavica
  • 2010
The clinical evidence, although limited, is at least consistent with the possibility that central μ‐opioid receptors may mediate anti‐emesis in humans, and it is possible that the role of μ‐OPioid agonists in anti-emesis may become clearer in the future as a result of the use of peripheral μ‐ipioid receptor antagonists.

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MNTX has been shown to improve oral-cecal transit times in opioid treated patients, induce laxation in chronic opioid users, and neither reverses the analgesic effects of morphine nor cause withdrawal symptoms, and seems to be well tolerated with limited or transient side effects.

Development and use of methylnaltrexone, a peripherally acting opioid antagonist, to treat side effects related to opioid use

Methylnaltrexone is the first peripherally acting opioid receptor antagonist to receive FDA approval and offers the therapeutic potential to block or reverse the undesired side effects of opioids that are mediated by receptors located in the periphery, without affecting analgesia or precipitating opioid withdrawal symptoms.
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