title: Targeting tachykinin receptors for the treatment of functional gastrointestinal disorders with a focus on irritable bowel syndrome.
abstract: BACKGROUND
  Tachykinins (TKs) are a family of endogenous peptides widely expressed in the central and in the peripheral nervous systems as well as in the gastrointestinal (GI) tract. They act as full agonists at three different membrane receptors neurokinin (NK) 1, NK2, and NK3, which are G protein-coupled receptors and in the GI tract are expressed both on neurons and effector cells.
  
  
  OBJECTIVE
  This article reviews the literature concerning the role of TKs in the GI tract function in physiological and pathological conditions and their potential relevance in the treatment of functional GI disorders with particular reference to irritable bowel syndrome (IBS). The efficacy of NK1 antagonists in chemotherapy-induced and postoperative nausea and vomiting is well established. While pharmacodynamic studies have reported conflicting and negative results concerning the effects of NK1 and of NK3 antagonists, respectively, on the GI tract function in humans, clinical studies applying the NK3 antagonist talnetant in IBS-D were negative. Pharmacodynamic studies applying NK2 antagonists have suggested a role for antagonism of NK2 receptors in modulation of GI chemical-induced altered motility and of stress-induced altered bowel habits. Clinical studies and in particular a recently completed Phase 2 study have reported that the NK2 antagonist ibodutant is effective and safe in treating symptoms of D-IBS, especially in females.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Corsetti
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Akyuz
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Tack
mesh_terms: D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D018039:Receptors, Tachykinin
keywords: NK1; NK2; NK3; ibodutant; nepadutant; tachykinins