Development of peripheral opioid antagonists' new insights into opioid effects

Mayo Clin Proc. 2008 Oct;83(10):1116-30. doi: 10.4065/83.10.1116.


The recent approval by the US Food and Drug Administration of 2 medications--methylnaltrexone and alvimopan--introduces a new class of therapeutic entities to clinicians. These peripherally acting mu-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient. Alvimopan, an orally administered medication, has been approved in the United States to facilitate recovery of gastrointestinal function after bowel resection and primary anastomosis. Clinical and laboratory studies performed during the development of these drugs have indicated that peripheral receptors mediate other opioid effects, including decreased gastric emptying, nausea and vomiting, pruritus, and urinary retention. Laboratory investigations with these compounds suggest that opioids affect fundamental cellular processes through mechanisms that were previously unknown. These mechanisms include modifications of human immunodeficiency virus penetration, tumor angiogenesis, vascular permeability, and bacterial virulence.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / physiopathology
  • Humans
  • Narcotic Antagonists / pharmacology*
  • United States


  • Narcotic Antagonists