New Generation Laxatives

Abstract

A significant proportion of chronic constipation patients are dissatisfied with their treatment. Recently, a number of new medicationshave been introduced for patients refractory to conventional laxatives, such as prucalopride, lubiprostone, linaclotide, andelobixibat. Prucalopride is a novel gastrointestinal prokinetic agent that acts as a 5-hydroxytryptamine type 4 (5-HT4) agonist. Compared with older nonselective 5-HT4 agonists, the higher selectivity of prucalopride for 5-HT4 receptors can reduce the risk ofsignificant adverse cardiovascular events. Prucalopride improves stool frequency and consistency, and reduces the need for rescuemedications. Lubiprostone, a chloride channel activator, increases the secretion of intestinal fluid, improves the stool frequency andconsistency, and reduces straining. Linaclotide, a guanylate cyclase-C agonist, is effective in treating patients with chronic constipationand its effect on visceral sensitivity, as shown mainly in animal studies, provides an attractive pharmaceutical option for patients with irritable bowel syndrome with constipation. Elobixibat is an ileal sodium-dependent bile acid transporter inhibitor thatblocks the enterohepatic circulation of bile acids, increasing the bile acid concentration in the intestine, which accelerates colonictransit and softens the stool. A phase III trial of the treatment of chronic constipation and irritable bowel syndrome with constipationis underway. The clinical application of new-generation laxatives will contribute to the management of chronic constipation refractoryto conventional laxatives.