The 5-HT4 antagonist R216073 does not affect gastric motor and sensory function in patients with functional dyspepsia.
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.


OBJECTIVE
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.
Van Lelyveld
N
N
Department of Gastroenterology, Gastrointestinal Research Unit, University Medical Centre Utrecht, Utrecht, The Netherlands.
Ter Linde
J
J
Baron
A
A
Mundt
M
M
Wajs
E
E
Samsom
M
M
D000328:Adult; D004311:Double-Blind Method; D004415:Dyspepsia / Q000503:physiopathology*; D005260:Female; D005502:Food; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects*; D012677:Sensation; D058832:Serotonin 5-HT4 Receptor Antagonists; D013997:Time Factors
D058832:Serotonin 5-HT4 Receptor Antagonists