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The pathophysiology of functional dyspepsia (FD), a clinical syndrome defined by chronic or recurrent upper abdominal pain/discomfort of unknown origin, is poorly understood. This lack of understanding has hindered efforts to develop effective treatments.
In a review article published in the August 2004 issue of Current Treatment Options in Gastroenterology, Vincenzo Stanghellini, MD, and colleagues reported on drugs that target upper gut dysmotility and sensory dysfunction, which are thought to be involved in the pathophysiology of FD. The drugs and drug classes discussed included antidopaminergics (eg, metoclopramide, domperidone, levosulpiride), erythromycin and related derivatives (motilides), κ-opioid receptor agonists, antidepressants (eg, tricyclic agents, selective serotonin [5-hydroxytryptamine; 5-HT] reuptake inhibitors), and 5-HT type 4 (5-HT4) receptor agonists (eg, tegaserod).
The authors noted that, because antidopaminergic agents enhance gastric motility, they can interfere with the absorption of a wide spectrum of drugs (eg, digoxin, theophylline, levodopa, cyclosporine). Antidopaminergic agents also evoke hyperprolactinemia. Erythromycin and motilides accelerate gastric emptying, but they have a stimulatory effect on fundic tone and are associated with tachyphylaxis, which impedes their long-term use.
Although κ-opioid receptor agonists may be helpful in the treatment of functional gastrointestinal disorders, they have not been studied extensively because of their antinociceptive properties; results of these studies have been inconclusive. Finally, 5-HT4 receptor agonists improve gastric emptying without increasing gastric fundus tone, which may contribute to symptom improvement.