Novel investigational drugs for constipation-predominant irritable bowel syndrome: a review

Expert Opin Investig Drugs. 2016;25(3):275-86. doi: 10.1517/13543784.2016.1142532. Epub 2016 Feb 4.

Abstract

Introduction: Constipation-predominant irritable bowel syndrome (IBS-C) is a functional gastrointestinal (GI) disorder with an unknown etiology. A number of the drugs tested for IBS-C have also been applied to chronic constipation and chronic idiopathic constipation. Unfortunately, due to severe adverse effects, many drugs envisioned for IBS-C had been withdrawn from the market. Nevertheless, a number of potential new agents for this indication are now under development.

Areas covered: The following review describes the most recently developed agents in preclinical as well as Phase 1 and Phase 2 clinical studies. Information was obtained from published literature, abstracts and the latest results found in Clinicaltrial.gov database. The authors put a special interest on glucagon-like peptide 1 analogue, bile acid modulators, serotonergic agents, guanylate cyclase C and cannabinoid antagonists.

Expert opinion: To enter the market, a newly-developed drug has to meet several criteria, such as good bioavailability or the absence of drug-related adverse events. Taking into account constipation and abdominal pain as the main symptoms in IBS-C, a novel successful drug is usually able to improve both at the same time. Four out of fifteen investigational drugs described in this paper belong to the serotonergic family and have a good prognosis to reach the market; still, more long-term clinical studies are warranted.

Keywords: GLP-1 analogue; bile acid transporter; cannabinoid; chloride channels; constipation-predominant irritable bowel syndrome; guanylate cyclase C; serotonin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abdominal Pain / drug therapy
  • Abdominal Pain / etiology
  • Animals
  • Constipation / drug therapy*
  • Constipation / etiology
  • Drug Design
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / pharmacology
  • Gastrointestinal Agents / therapeutic use
  • Humans
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / physiopathology

Substances

  • Drugs, Investigational
  • Gastrointestinal Agents