Role of prucalopride, a serotonin (5-HT₄) receptor agonist, for the treatment of chronic constipation

Banny S Wong, Noriaki Manabe, Michael Camilleri

Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota, USA

Abstract: Constipation affects up to a quarter of the population in developed countries and is associated with poor quality of life and significant economic burden. Many patients with chronic constipation are dissatisfied with current therapy due to lack of long-term efficacy or side effects. Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT₄) agonists have been associated with significant interactions with other receptors (5-HT_1B, 5-HT_1D, and 5-HT_2B for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market. Prucalopride is a novel gastrointestinal prokinetic agent. It acts as a high affinity, highly-selective 5-HT₄ agonist. Its efficacy in patients with chronic constipation has been demonstrated in several phase II and phase III clinical trials showing significant improvements in bowel transit, bowel function, gastrointestinal symptoms, and quality of life, with benefit maintained for up to 24 months in open label, multicenter, follow-up studies. Prucalopride’s high selectivity for the 5-HT₄ receptor may explain its favorable safety and tolerability profiles, even in elderly subjects with stable cardiovascular disease. Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments.

Keywords: prucalopride, 5-HT₄ agonist, serotonin agonist, efficacy, prokinetic