Prucalopride: safety, efficacy and potential applications

Abstract

Chronic constipation is a very common functional gastrointestinal disorder which can be associated with significant impairments in quality of life for some people with the condition. Its management has, traditionally, been based on dietary and lifestyle changes and the use of a variety of laxative agents. The evidence base for the efficacy of the latter is, in many cases, slim. Not surprisingly, many patients remain dissatisfied with laxatives thus leading to the development of more pharmacological approaches. Among these approaches is the use of prokinetic agents; while prior molecules have been troubled by lack of selectivity and cardiac side effects, the new agent, prucalopride, appears to be highly selective for the serotonin 5-HT4 receptor and is, therefore, a potent stimulator of gut motility. In three large pivotal randomized controlled trials, prucalopride has been effective in relieving the cardinal symptoms of chronic constipation; these effects have been sustained in open-label follow up for as long as 18 months. The safety profile has been encouraging and, especially so, the absence of arrhythmogenic potential. Studies in men, in constipation-predominant irritable bowel syndrome and in other motor disorders are eagerly awaited.