Cisapride
Gastroprokinetic agent withdrawn due to cardiac risks.
Cisapride is a gastroprokinetic agent that increases motility in the upper gastrointestinal tract. It acts as a selective serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic, stimulating acetylcholine release in the enteric nervous system. Discovered by Janssen Pharmaceuticals in 1980, it was sold under the trade names Prepulsid and Propulsid. Due to serious cardiac side-effects and links to children's deaths, it has been withdrawn or had its indications limited in many countries.
- Discovered
- 1980
- Discoverer
- Janssen Pharmaceuticals
- Field
- Pharmacology
- Mechanism
- 5-HT4 receptor agonist, parasympathomimetic
- Known for
- Treatment of GERD and diabetic gastroparesis; withdrawn due to cardiac side-effects
Lore & Background
Serious cardiac side-effects, particularly long QT syndrome leading to arrhythmias, prompted regulatory action. The U.S. FDA issued a warning letter, and cisapride was voluntarily removed from the U.S. market on July 14, 2000. Its use in Europe was also limited, and it was banned in India and the Philippines in 2011. Despite this, cisapride remains available in the United States and Canada for veterinary use, treating megacolon in cats and GI stasis in rabbits.
Reader's Guide
Cisapride's significance lies in its role as a prokinetic agent that advanced understanding of serotonin's role in gastrointestinal motility. However, its legacy is overshadowed by its cardiac toxicity, which led to its withdrawal from human use in many countries. The drug's interaction with the hERG channel, prolonging the QT interval, became a cautionary example in drug development. Its continued veterinary use highlights a risk-benefit balance where animal patients may tolerate the drug better. The discovery that the (+) enantiomer has major effects with fewer side-effects points to potential for safer derivatives, though none have fully replaced cisapride in human medicine. The case underscores the importance of post-marketing surveillance and the need to assess cardiac risks in drugs affecting serotonin receptors.
Did You Know?
- Cisapride was discovered by Janssen Pharmaceuticals in 1980.
- The (+) enantiomer has the major pharmacologic effects and does not induce many detrimental side-effects of the racemic mixture.
- Cisapride is still used in veterinary medicine for megacolon in cats and GI stasis in rabbits.
Frequently Asked Questions
Who created Cisapride and when?
Cisapride was developed by the Belgian pharmaceutical company Janssen Pharmaceuticals and first brought to market in 1980. It entered the world as a gastroprokinetic drug designed to boost movement in the upper digestive tract.
How does Cisapride actually work in the body?
It targets serotonin 5-HT4 receptors in the gut and also nudges the parasympathetic nervous system to release acetylcholine. Together, these actions speed up peristalsis in the upper gastrointestinal tract.
What conditions was Cisapride prescribed for?
Doctors commonly used it to manage gastroesophageal reflux disease (GERD) and diabetic gastroparesis, both of which involve sluggish stomach emptying.
Why was Cisapride pulled from the market?
Serious cardiac arrhythmias and a tragic link to pediatric deaths forced regulators in numerous countries to either withdraw the drug entirely or sharply restrict its approved uses.
Under what brand names was Cisapride sold?
You'll find it listed in old pharmacy records as either Prepulsid or Propulsid, depending on the market.
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