Gastroprokinetic agent

A gastroprokinetic agent, gastrokinetic, or prokinetic, is a type of drug which enhances gastrointestinal motility by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm. They are used to relieve gastrointestinal symptoms such as abdominal discomfort, bloating, constipation, heart burn, nausea, and vomiting. They are used to treat a number of gastrointestinal disorders, including irritable bowel syndrome, gastritis, acid reflux disease, gastroparesis, and functional dyspepsia.

Most of these drugs are grouped under ATC code A03F.

Pharmacokinetics

These drugs may increase acetylcholine concentrations by antagonizing the D₂ receptor which inhibits acetylcholine release, or by inhibiting the enzyme acetylcholinesterase which metabolizes acetylcholine. Higher acetylcholine levels increase gastrointestinal peristalsis and further increase pressure on the lower esophageal sphincter, thereby stimulating gastrointestinal motility, accelerating gastric emptying, and improving gastro-duodenal coordination.

Some of these drugs may or may not have affinity for the 5-HT₄ receptor depending on their class such as some benzamides like cisapride and mosapride which are 5-HT₄ agonists. The affinity of cisapride for 5-HT₄ receptors in the heart has been implicated as a potential cause of cardiac arrhythmias.^[1] Other molecules, including macrolides such as mitemcinal and Erythromycin, appear to have high 5-HT₄ affinity as well, although limited data exists as this property was an unexpected outcome of off-label use in the clinic.

Examples

• Benzamide
• Cisapride
• Domperidone
• Erythromycin
• Itopride
• Metoclopramide
• Prucalopride
• Renzapride
• Tegaserod
• Mitemcinal

References

Further reading

• Hardman JG, Limbird LE, Gilman AG. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill, 2001. ISBN 0-07-135469-7.