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

  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},
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… 

Prevention of apomorphine- or cisplatin-induced emesis in the dog by a combination of methylnaltrexone and morphine

The results support the hypothesis that the emetic effect of morphine is peripheral and its antiemetic action is central and in combination, MNTX and morphine may have a clinical role in the treatment of chemotherapy-induced emesis.

Efficacy of Methylnaltrexone Versus Naloxone for Reversal of Morphine‐Induced Depression of Hypoxic Ventilatory Response

Data show that MNTX is not as effective as naloxone for reversal of morphine-mediated depression of respiration during acute hypoxia.

The Cannabinoid Agonist WIN55,212-2 Suppresses Opioid-induced Emesis in Ferrets

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.

Subcutaneous methylnaltrexone may have clinical utility in treating opioid-induced constipation and reducing morphine-induced unpleasant subjective symptoms and pharmacokinetic data after subcutaneous drug injection were studied.

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.

A review of methylnaltrexone, a peripheral opioid receptor antagonist, and its role in opioid-induced constipation

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.



Emetic and antiemetic effects of opioids in the dog.

Naloxone antagonizes narcotic self blockade of emesis in the cat.

The present differentiation by naloxone of the emetic and antiemetic properties of narcotic agents placed in the cerebrospinal fluid indicates that the opposing narcotic actions are exercised at different sites in the brain and that the narcotic receptor specificity of the chemoreceptor trigger zone does not encompass theEmetic action of apomorphine.


The reduction in the mortality of morphine poisoning in mice by N -allyl-normorphine further demonstrates the effectiveness of this substance as an antidote against morphine.

Multiple morphine and enkephalin receptors and the relief of pain.

Recent work indicates that the receptors responsible for many opiate side effects differ from those producing analgesia, implying that analgesics lacking these unwanted actions may be possible.

Independent central and peripheral mediation of morphine-induced inhibition of gastrointestinal transit in rats.

Peripherally selective antagonists such as quaternary naltrexone may be useful in reversing morphine-induced inhibition of gastrointestinal transit without affecting analgesia.

The central and peripheral influences of opioids on gastrointestinal propulsion.

This article represents an effort to lay out a framework against which to assess the relative roles of central and peripheral opioid-specific mechanisms affecting gastrointestinal propulsion.