Cisapride

Cisapride is a gastroprokinetic agent that was historically used to treat gastroesophageal reflux disease and gastroparesis. It acts as a selective serotonin 5-HT4 receptor agonist, which enhances the release of acetylcholine in the enteric nervous system and promotes more coordinated gastric and intestinal motility.

The drug’s prokinetic effect stems from stimulation of 5-HT4 receptors in the GI tract, leading to increased smooth muscle activity and improved transit of contents from the stomach through the intestines. This mechanism underlay its use for conditions characterized by reduced GI motility.

Cisapride gained widespread use but was found to carry a risk of serious cardiac events, notably QT interval prolongation and torsades de pointes. Regulatory agencies and manufacturers subsequently withdrew it from the market in the United States in 2000 and in many other countries due to these safety concerns. The risk is heightened when cisapride is used with certain drugs or in patients with risk factors such as electrolyte disturbances or congenital long QT syndrome.

Pharmacokinetically, cisapride is taken orally and is extensively metabolized by the liver, producing an active metabolite called norcisapride. Its clearance is affected by liver enzyme activity, particularly cytochrome P450 3A4, making drug interactions a key safety concern. In practice, cisapride is no longer approved for general use in many regions, and where it remains available it is typically under strict controls or for restricted indications. Clinicians now rely on alternative prokinetic therapies where appropriate.