Linaclotide acetate. Guanylate cyclase C receptor agonist, treatment of irritable bowel syndrome, treatment of constipation

Linaclotide acetate (MD-1100) is a novel, orally administered agent currently in development for the treatment of gastrointestinal disorders, including irritable bowel syndrome with predominant constipation (IBS-C) and chronic constipation. This 14-amino-acid peptide is a first-in-class compound that acts as an agonist of human guanylate cyclase C (GC-C), a transmembrane protein located in intestinal epithelial cells. Activation of intestinal GC-C induces secretion of fluid, sodium and bicarbonate in the intestinal lumen. In animal studies, linaclotide accelerated gastrointestinal transit, decreased stool consistency and decreased visceral pain measured by surrogate markers. In clinical studies in healthy volunteers and patients with chronic constipation or IBS-C, linaclotide had a significant effect on stool consistency, ease of passage of stools and increase in stool frequency, as well as improving bowel function and abdominal discomfort. In all animal and human studies, linaclotide appeared to be safe and well tolerated, with minimal bioavailability. Further randomized, controlled trials of clinical efficacy and safety in larger patient populations are warranted.