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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Linaclotide-a Novel Secretagogue in the Treatment of Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation

Author(s): Shivani Sharma, Tina Sharma, Richa Dhingra, Prince Tomar, Sukhminder Singh, Manav Malhotra and T. R. Bhardwaj

Volume 13, Issue 11, 2013

Page: [1685 - 1690] Pages: 6

DOI: 10.2174/1389557511313110011

Price: $65

Abstract

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are highly prevalent gastrointestinal disorders. Traditional symptoms based therapies had somewhat limited success and efficacy in addressing the disorders. Recently, linaclotide emerged as novel peptide capable of improving abdominal symptoms in patients suffering from IBS-C and CIC. Guanylate cyclase C (GC-C) receptor a multi domain protein, found to be molecular target for linaclotide which acts by activating GC-C receptor on the apical surface of intestinal epithelial cells. Binding of linaclotide to GC-C receptor triggers the elevation of second messenger cGMP that elicits fluid secretion into intestinal cells which play a critical role in maintaining homeostasis through cystic fibrosis transmembrane conductance regulator (CFTR). Data from Phase and clinical trials demonstrated that linaclotide seems to produce a statistically significant increase in stool frequency, improved straining, decreased abdominal pain and discomfort.

Keywords: CIC, cGMP, guanylate cyclase C, homeostasis, IBS-C, Linaclotide.

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