Cisapride: What can we learn from the rise and fall of a prokinetic?

Cisapride, the prototype serotonergic agent, evolved from a body of research that defined the key roles of serotonergic receptors in gastrointestinal motor and sensory function. Impressed by its in vitro properties and encouraged by clinical trial data, cisapride became the drug of choice for the treatment of a wide range of motility disorders and clinicians appeared impressed by its efficacy and comfortable with its side-effect profile. Once serious cardiac events began to be reported in association with cisapride therapy, dark clouds rapidly gathered and soon enveloped the drug, leading to its widespread withdrawal from markets. What lessons can we learn from the story of cisapride? How can its brief but spectacular rise and equally sensational demise inform the development of new drugs which are so sorely needed in the management of motility and functional gastrointestinal disorders? This review explores the background to the development of cisapride, its history in clinical trials and the experience with adverse events and, in so doing, attempts to identify lessons for the future in the therapeutics of enteric neuromodulatory drugs.