Development of a Gastrointestinal Prokinetic: Pharmacology of Cisapride

The synthesis of benzamides derived from 1-substituted-3-methoxy or 3-hydroxy-4-piperidinamine resulted in the selection of a substituted benzamide, cisapride, which displays potent gastrokinetic properties. Pharmacological studies showed that cisapride improves both motility and transit of the oesophagus, the stomach, the small and large intestines. Moreover it markedly improves gastropyloroduodenal coordination. The gastrokinetic effects of cisapride are largely due to an enhanced release of acetylcholine from cholinergic nerves in the myenteric plexus (plexus of Auerbach) along the digestive tract. This explains why the therapeutic efficacy of cisapride reaches from the oesophagus into the large intestine.