gastroparesis in a randomized, double blind trial was studied. After 6 weeks of therapy, there was significant symptomatic improvement (5). Another study compared cisapride and metoclopramide (6). The results indicated that cisapride was significantly better than equivalent doses of metoclopramide in accelerating or normalizing gastric emptying, and more patients reported symptomatic improvement on cisapride compared with metoclopramide and placebo. Other studies have demonstrated no significant symptomatic improvement. Cisapride was compared to placebo over a 6-week period study and authors documented an improvement after cisapride treatment in solid-phase gastric emptying and pain, but no change in the other symptoms related to gastroparesis (7). Similarly, a randomized, double blind, placebo-controlled study reported that cisapride accelerated gastric emptying but failed to show any significant symptomatic improvement (8). However, cisapride was withdrawn from the market in the United States in 2000, as it produces severe adverse cardiac effects, leaving the market open to novel, safe and efficacious treatments.
Several new and more selective 5-HT4 agonists are in development or under preclinical investigation as prokinetics for the treatment of functional dyspepsia. As other 5-HT4 agonists, most of them are still substituted benzamides like zacropride (2], renzapride (31 or mosapride (41. These compounds often have some dopamine D2 and 5-HT3 receptor antagonist properties.
The recent cloning of the human 5-HT4 receptor has given rise to a series of more selective and attractive agents. Tegaserod (5), a 5-HT4 partial agonist, already approved for the treatment of Irritable Bowel Syndrome (IBS), is under evaluation for dyspepsia. In animals and healthy volunteers, it has been shown to improve gastric emptying (9).
Similarly YM-53389 (6), a very selective 5-HT4 receptor agonist, improves upper gastrointestinal propulsion in animals and is under consideration for clinical trials in dyspeptic patients (10).
TKS-159 (7) is also a novel selective 5-HT4 selective agonist (11). It stimulates both antral and duodenal contractions and acccelerates gastric emptying, these effects being blocked by a 5-HT4 antagonist, SDZ-205-557 (8).
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Gastroesophageal reflux disease is the medical term for what we know as acid reflux. Acid reflux occurs when the stomach releases its liquid back into the esophagus, causing inflammation and damage to the esophageal lining. The regurgitated acid most often consists of a few compoundsbr acid, bile, and pepsin.