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The 5-HT4 antagonist R216073 does not affect gastric motor and sensory function in patients with functional dyspepsia
N Van Lelyveld1, J Ter Linde, A Baron
1Department of Gastroenterology, Gastrointestinal Research Unit, University Medical Centre Utrecht, Utrecht, The Netherlands.
Background:
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.
Aim:
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.
Methods:
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.
Results:
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.
Conclusions:
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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