Identifying and Treating Opioid Side Effects: The Development of Methylnaltrexone

  title={Identifying and Treating Opioid Side Effects: The Development of Methylnaltrexone},
  author={Jonathan Moss},
  • J. Moss
  • Published 2019
  • Medicine
  • Anesthesiology
Methylnaltrexone Reverses Chronic Opioid-induced Constipation: A Randomized, Controlled Trial. By Yuan CS, Foss JF, O’Connor M, Osinski J, Karrison T, Moss J, Roizen MF. JAMA 2000; 130:142–8. Reprinted with permission. Context: Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient. Objective: To… 

Recent Chemical and Pharmacological Developments on 14-Oxygenated-N-methylmorphinan-6-ones

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Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects

A drug delivery approach for restricting the passage of small molecules across the blood-brain barrier is developed and it is demonstrated that the mu-opioid receptors in the central nervous system have a fundamental role in precipitating opioid-induced constipation.

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Successive treatment with naltrexone induces epithelial-mesenchymal transition and facilitates the malignant biological behaviors of bladder cancer cells.

Investigation of the effects of successive treatment with clinically relevant doses of naltrexone on the malignant biological behaviors of bladder cancer cells found that successive treatment may be favorable for the progression of bladder tumors by activating the PI3K/AKT signaling pathway and inducing EMT.

β-endorphin at the intersection of pain and cancer progression: Preclinical evidence



Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial.

It is demonstrated that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages and may have clinical utility in managing opioid-induced constipation.

Methylnaltrexone for opioid-induced constipation in advanced illness.

Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation and did not appear to affect central analgesia or precipitate opioid withdrawal.

Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients.

Subcutaneous methylnaltrexone was efficacious in rapidly inducing laxation and was generally well tolerated in patients with advanced illness and OIC, and there was no change in pain scores or evidence of central opioid withdrawal.

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer.

This unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTx are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression.

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.

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

If morphine‐induced emesis is mediated by receptors available to a quaternary antagonist (perhaps on the peripheral side of the blood‐brain barrier), MNTX may prevent opioid‐inducedEmesis, and data indicate that opioid‐ induced emesis might be prevented without affecting analgesia.

Methylnaltrexone Antagonizes Opioid-Mediated Enhancement of HIV Infection of Human Blood Mononuclear Phagocytes

Whether the quaternary opioid antagonist methylnaltrexone (MNTX), now in phase III clinical trials for opioid-induced constipation, reverses the opioid-mediated enhancement of HIV infection of macrophages at clinically relevant doses is determined.

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.