Abstract
Serotonin and the 5-HT4 receptor play an important role in gastrointestinal motor and sensory functions. While 5-HT4 agonists are known for their prokinetics properties, the effect of 5-HT4 antagonists on upper gastrointestinal functions is largely unknown. To assess the effect of a 5-HT4 receptor antagonist (R216073) on gastric relaxation and visceral sensitivity in patients with functional dyspepsia. Secondly, the influence of a functional polymorphism in the gene encoding the serotonin transport protein on drug response was determined. A double-blind, randomized, placebo-controlled, two-period crossover study was performed in 20 functional dyspepsia patients. The effect of a single dose of 2,000 mg R216073 on gastric relaxation and sensitivity was tested using three-dimensional ultrasonography and a nutrient drinktest. R216073 did not affect partial gastric volumes or upper abdominal sensations scored during three-dimensional ultrasonography (P > 0.05). The maximum tolerated volume or upper abdominal sensations induced by the drinktest were not affected by R216073 (P > 0.05). The serotonin transport protein promoter polymorphism was not associated with any of the end-points of the study. A single dose of R216073 had no effect on fundic relaxation, drinking capacity, or upper abdominal symptoms in patients with functional dyspepsia.
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