What is the mechanism of Cisapride Monohydrate?

Cisapride monohydrate is a prokinetic agent used to enhance gastrointestinal motility. Its primary mechanism of action involves the enhancement of the release of acetylcholine at the myenteric plexus. This neurotransmitter plays a key role in stimulating muscle contractions in the gastrointestinal tract, thereby promoting the movement of contents through the digestive system.

The action of cisapride monohydrate is largely mediated through its agonistic effect on serotonin 5-HT4 receptors. By activating these receptors, cisapride increases the release of acetylcholine from the enteric neurons. This, in turn, enhances peristalsis, the wave-like muscle contractions that move food through the digestive tract. Unlike some other prokinetic agents, cisapride does not have a direct stimulant effect on smooth muscle but rather enhances the physiological release of neurotransmitters that naturally promote motility.

Additionally, cisapride has been shown to have some affinity for serotonin 5-HT3 receptors, although its primary prokinetic effects are attributed to the 5-HT4 receptor activation. The stimulation of 5-HT4 receptors facilitates a coordinated contraction of the gastrointestinal muscles, enhancing the transit of gastrointestinal contents. This makes cisapride particularly effective in treating conditions associated with reduced gastrointestinal motility, such as gastroesophageal reflux disease (GERD), constipation, and certain types of gastroparesis.

It is important to note that while cisapride monohydrate was initially approved for several gastrointestinal disorders, its use has become highly restricted due to concerns about its safety profile. Cisapride has been associated with serious cardiac side effects, including QT interval prolongation and arrhythmias. These risks have led to its withdrawal from the market in many countries and its use being limited to specific cases where the potential benefits outweigh the risks and where other treatments have proven ineffective.

In summary, the mechanism of cisapride monohydrate involves the enhancement of acetylcholine release at the myenteric plexus through the stimulation of serotonin 5-HT4 receptors. This action promotes gastrointestinal motility by enhancing peristalsis, making it effective in treating conditions characterized by slowed gastrointestinal transit. However, due to its potential for serious cardiac side effects, its use is now highly restricted and monitored closely.