title: Novel investigational drugs for constipation-predominant irritable bowel syndrome: a review.
abstract: BACKGROUND
  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 Unfortunately, due to severe adverse effects, many drugs envisioned for IBS-C had been withdrawn from the market.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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Biochemistry, Faculty of Medicine , Medical University of Lodz , Lodz , Poland.
authors.forename: Paula
authors.initials: P
authors.lastname: Mosińska
authors.affiliation: a Department of Biochemistry, Faculty of Medicine , Medical University of Lodz , Lodz , Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Salaga
authors.affiliation: a Department of Biochemistry, Faculty of Medicine , Medical University of Lodz , Lodz , Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D015507:Drugs, Investigational; D005765:Gastrointestinal Agents
keywords: GLP-1 analogue; bile acid transporter; cannabinoid; chloride channels; constipation-predominant irritable bowel syndrome; guanylate cyclase C; serotonin