Opioids have been used medicinally and recreationally for thousands of years. The clinical use of opioids for gastrointestinal conditions has been limited by central nervous system side effects. A new generation of peripheral opioid receptor ligands free of central nervous system side effects is being developed. Clinical trials with the peripherally acting mu opioid receptor antagonists’ alvimopan and N-methylnaltrexone show promise for improving postoperative ileus- and opioid-induced constipation. Likewise, preliminary studies with the peripherally acting kappa opioid agonist fedotozine showed promise in the treatment of irritable bowel syndrome (IBS) and functional dyspepsia. Further studies are on hold presumably due to lack of efficacy in subsequent studies. However, clinical studies are underway for newer kappa opioid agonists such as asimadoline and ADL 10-0101.

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