Emerging treatments in Neurogastroenterology: Perspectives of guanylyl cyclase C agonists use in functional gastrointestinal disorders and inflammatory bowel diseases.

Background Functional gastrointestinal disorders ( FGID) and inflammatory bowel diseases ( IBD) are the most frequent pathologic conditions affecting the gastrointestinal ( GI) tract and both significantly reduce patients' quality of life. Recent studies suggest that guanylyl cyclase C ( GC-C) expressed in the GI tract constitutes a novel pharmacological target in the treatment of FGID and IBD. Endogenous GC-C agonists - guanylin peptides: guanylin and uroguanylin, by the regulation of water and electrolyte transport, are involved in the maintenance of homeostasis in the intestines and integrity of the intestinal mucosa. Linaclotide, a synthetic agonist of GC-C was approved by Food and Drug Administration and European Medicines Agency as a therapeutic in constipation-predominant irritable bowel syndrome ( IBS-C) and chronic idiopathic constipation (CIC). Lately, several preclinical and clinical trials focused on assessment of therapeutic properties of synthetic agonists of uroguanylin, plecanatide, and SP-333. Plecanatide is currently tested as a potential therapeutic in diseases related to constipation and SP-333 is a promising drug in ulcerative colitis treatment. Purpose Here, we discuss the most recent findings and future trends on the development of GC-C agonists and their use in clinical trials. [ABSTRACT FROM AUTHOR]