The active ingredient cisapride is one of the prokinetics that increase motility of the gastrointestinal tract. The active ingredient causes severe cardiac side effects and has therefore been withdrawn from the market in many countries. Its use is not recommended; safer drugs from the prokinetic group are available.
What is cisapride?
Cisapride belongs to the group of prokinetics. Prokinetics are agents that promote motility, or mobility, of the gastrointestinal tract. It has been withdrawn from the market in many countries due to severe side effects, as it causes cardiac arrhythmias and prolongs the QT interval. Chemically, it is a derivative of benzamide. The formula is C23H29ClFN3O4. It was withdrawn from the market in the U.S. in 2000, followed by a suspension of approval in Germany as well. However, it is still available in some countries. It should only be taken under caring consideration.
Pharmacologic effect
Cisapride is a parasympathomimetic, meaning that it enhances the action of the parasympathetic nervous system. The parasympathetic nervous system is a part of the autonomic nervous system and the antagonist of the sympathetic nervous system. The substance cisapride stimulates serotinin 5HT4 receptors. As a result of this stimulation, the receptors cause a release of the neurotransmitter acetylcholine. Acetylcholine plays a central role in stimulus transmission. It is released into the synaptic cleft and interacts with receptors on the postsynaptic membrane. As a result, the membrane of the target cell changes its ion permeability, which can trigger either excitation (depolarization) or inhibition (hyperpolarization) of the target cell. When the active ingredient cisapride is used, there is an increase in motility and increased peristalsis as a result of the acetylcholine. Thus, it has an overall prokinetic effect. As a side effect, a proarrhythmic influence on the heart is known, whereby a frequent occurrence of the so-called long-QT syndrome has been observed with cisapride. Long-QT syndrome is a disease of the heart belonging to the group of channelopathies, in which a pathologically prolonged QT interval occurs. If the long-QT syndrome occurs as a result of administration of cisapride, it is a secondary, i.e. acquired, QT syndrome. As a result of the side effect, the drug has been withdrawn from the market in many countries. The bioavailability of cisapride is about 30-40%, the drug is present in the blood mainly bound to plasma proteins, the plasma half-life is about ten hours. Cisapride is metabolized mainly in the liver, via the cytochrome P450 system, and in the intestine. The drug is excreted exclusively by the kidney and bile.
Medicinal use and application
The drug is used in reflux esophagitis, general motility disorders of the gastrointestinal tract, gastric paralysis, and constipation. The indications are derived from the pharmacological properties of cisapride, and the area of action is exclusively the gastrointestinal tract. Reflux esophagitis is an inflammation of the esophagus caused by reflux (backflow) of acidic gastric juice. Contraindications are cardiac arrhythmias, as well as tachycardia. The contraindications are due to the severe cardiac side effects of cisapride.
Risks and side effects
Risks and side effects include cardiac arrhythmias and the aforementioned prolongation of the QT interval. The side effects are drastic and can sometimes be fatal. The drug or active ingredient has been withdrawn from the market in many countries because the risks associated with its use have been deemed too high. The use of cisapride is not recommended, since other agents with fewer side effects are available from the group of prokinetics, which are not inferior to cisapride in terms of efficacy.
