Review article: 5‐hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications

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Abstract
Serotonin (5‐hydroxytryptamine; 5‐HT) is found in the enteric nervous system where it has been implicated in controlling gastrointestinal motor function. A number of receptor or recognition sites have been identified in the gut, but recently most attention has focused on the 5‐HT3 and 5‐HT4 receptors. The functional role of the 5‐HT3 receptor remains incompletely understood, but it is probably involved in the modulation of colonic motility and visceral pain in the gut. A number of selective 5‐HT3 antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride. While the substituted benzamide prokinetics (for example, metoclopramide, cisapride) also block 5‐HT3 receptors in high concentrations, their prokinetic action is believed to be on the basis of their agonist effects on the putative 5‐HT4 receptor. Some 5‐HT3 antagonists have 5‐HT4 agonist activity (for example, renzapride, zacopride) and others do not (for example, ondansetron, granisetron), while tropisetron in high concentrations is a 5‐HT3 antagonist. Based on the pharmacological data, it has been suggested that specific 5‐HT antagonists and agonists may prove to be beneficial in a number of gastrointestinal disorders including the irritable bowel syndrome, functional dyspepsia, non‐cardiac chest pain, gastrooesophageal reflux and refractory nausea. In this review, the rationale for the use of these compounds is discussed, and the available experimental evidence is summarized.