5-HT₄ receptor agonist treatment of chronic constipation

Chronic constipation and irritable bowel syndrome (IBS) with constipation affect patient quality of life and are associated with a high healthcare expenditure. Conventional therapies for chronic constipation have limited effectiveness. New-generation, selective 5-HT₄ receptor agonists are effective for chronic constipation, but none are currently approved in the U.S.; prucalopride is approved for the treatment of chronic constipation in Europe. The 5-HT₄ receptor agonist velusetrag is being developed for chronic constipation and IBS with constipation; it has high selectivity and affinity for the 5-HT₄ receptor. Velusetrag accelerates colonic transit in a dose-related manner, with a dose of 30 mg daily being the most effective over 9 days of treatment in healthy controls. In patients with chronic constipation, velusetrag increased spontaneous bowel movements after 4 weeks of therapy, with no serious cardiac events reported. Velusetrag has shown great promise, and further studies in chronic constipation and IBS with constipation are warranted.