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Targeting tachykinin receptors for the treatment of functional gastrointestinal disorders with a focus on irritable bowel syndrome
Author(s) -
Corsetti M.,
Akyuz F.,
Tack J.
Publication year - 2015
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12616
Subject(s) - irritable bowel syndrome , medicine , nk1 receptor antagonist , aprepitant , tachykinin receptor , nausea , antagonist , gastrointestinal tract , receptor , vomiting , pharmacology , gastroenterology , substance p , neuropeptide , antiemetic
Abstract 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.