Linaclotide-a novel secretagogue in the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.

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 II and III clinical trials demonstrated that linaclotide seems to produce a statistically significant increase in stool frequency, improved straining, decreased abdominal pain and discomfort.

• Authors: Shivani Sharma, Tina Sharma, Richa Dhingra, Prince Tomar, Sukhminder Singh, Manav Malhotra, T R Bhardwaj
• Journal: Mini reviews in medicinal chemistry (Mini Rev Med Chem) Vol. 13 Issue 11 Pg. 1685-90 (Oct 2013) ISSN: 1875-5607 [Electronic] Netherlands
• PMID: 24001336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• Cystic Fibrosis Transmembrane Conductance Regulator
• Receptors, Guanylate Cyclase-Coupled
• Cyclic GMP
• linaclotide

Topics

• Chronic Disease
• Clinical Trials as Topic
• Constipation (complications, drug therapy)
• Cyclic GMP (metabolism)
• Cystic Fibrosis Transmembrane Conductance Regulator (metabolism)
• Half-Life
• Humans
• Irritable Bowel Syndrome (complications, drug therapy)
• Peptides (chemistry, pharmacokinetics, therapeutic use)
• Receptors, Guanylate Cyclase-Coupled (antagonists & inhibitors, metabolism)