Investigational opioid antagonists for treating opioid-induced bowel dysfunction

Expert Opin Investig Drugs. 2018 Mar;27(3):235-242. doi: 10.1080/13543784.2018.1420778. Epub 2017 Dec 26.


Introduction: Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC.

Areas covered: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued.

Expert opinion: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

Keywords: Clinical trial; constipation; mu-opioid receptor antagonists; opioid-induced constipation.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Constipation / chemically induced
  • Constipation / drug therapy*
  • Drug Design
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Humans
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use*
  • Pain / drug therapy
  • Quality of Life
  • Receptors, Opioid, mu / antagonists & inhibitors


  • Analgesics, Opioid
  • Drugs, Investigational
  • Narcotic Antagonists
  • Receptors, Opioid, mu