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.
Activation of a wide range of serotonin receptors by serotonin itself or by certain prokinetic drugs results in enhanced gastrointestinal motility. Other prokinetic drugs may increase acetylcholine concentrations by stimulating the M1 receptor which causes 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.
The 5-HT4 receptor is thought to play a significant role in both the physiology and pathophysiology of GI tract motility. Therefore, 5-HT4 receptors have been identified as potential therapeutic targets for diseases related to GI dysmotility such as chronic constipation. Some of these prokinetic agents, such as mosapride and cisapride, classic benzamides, have only moderate affinity for 5HT4 receptors. In recent years, it has become clear that the selectivity profile is a major determinant of the risk-benefit profile of this class of agent. As such, the relatively poor selectivity profile of cisapride versus other receptors (especially hERG [human ether-a-go-go K+] channels) contributes to its potential to cause cardiac arrhythmias. Prucalopride, a first in class benzofuran, is a selective, high affinity serotonin (5-HT4) receptor agonist that stimulates colonic mass movements, which provide the main propulsive force to defecation. SSRIs have been found to have prokinetic actions on the small intestine.
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