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Peripheral opioids for functional GI disease: a reappraisal.
1Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. alembo@bibmc.harvard.edu
Digestive Diseases (Basel, Switzerland)
|May 16, 2006
Summary
New peripheral opioid receptor ligands offer gastrointestinal relief without central nervous system side effects. Clinical trials show promise for conditions like opioid-induced constipation and irritable bowel syndrome.
Area of Science:
- Pharmacology
- Gastroenterology
- Drug Development
Background:
- Opioids have a long history of medicinal and recreational use.
- Central nervous system side effects limit the clinical application of traditional opioids for gastrointestinal (GI) conditions.
- A novel class of peripherally acting opioid receptor ligands is emerging to overcome these limitations.
Purpose of the Study:
- To review the development and clinical potential of peripherally acting opioid receptor ligands for GI disorders.
- To evaluate the efficacy of specific mu opioid receptor antagonists and kappa opioid receptor agonists.
Main Methods:
- Review of clinical trials and preliminary studies involving peripherally acting opioid ligands.
- Focus on agents targeting mu and kappa opioid receptors in the periphery.
- Analysis of outcomes for conditions such as postoperative ileus, opioid-induced constipation, irritable bowel syndrome, and functional dyspepsia.
Main Results:
- Peripherally acting mu opioid receptor antagonists (alvimopan, N-methylnaltrexone) show promise in managing postoperative ileus and opioid-induced constipation.
- Preliminary studies of the kappa opioid receptor agonist fedotozine indicated potential for irritable bowel syndrome and functional dyspepsia, though further studies were halted.
- Ongoing clinical studies are evaluating newer kappa opioid agonists (asimadoline, ADL 10-0101).
Conclusions:
- Peripherally acting opioid receptor ligands represent a promising therapeutic strategy for GI conditions by avoiding central nervous system side effects.
- While some agents have demonstrated clinical utility, further research and development are ongoing for newer compounds, particularly kappa opioid agonists.