Targeting tachykinin receptors for the treatment of functional gastrointestinal disorders with a focus on irritable bowel syndrome

Background Tachykinins ( TK s) 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, NK 2, and NK 3, which are G protein‐coupled receptors and in the GI tract are expressed both on neurons and effector cells. Purpose This article reviews the literature concerning the role of TK s 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 NK 1 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 NK 1 and of NK 3 antagonists, respectively, on the GI tract function in humans, clinical studies applying the NK 3 antagonist talnetant in IBS ‐D were negative. Pharmacodynamic studies applying NK 2 antagonists have suggested a role for antagonism of NK 2 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 NK 2 antagonist ibodutant is effective and safe in treating symptoms of D‐ IBS , especially in females.