The influence of the novel 5-HT1A agonist R137696 on the proximal stomach function in healthy volunteers.
As fundic dysaccommodation represents one of the pathophysiological mechanisms underlying functional dyspepsia, gastric relaxant agents may serve as a new treatment of this disorder. Previous studies have suggested the involvement of 5HT1 receptors in the control of gastric tone. Our aim was to study the effect of R137696, a novel 5HT1A agonist, on fundus sensorimotor function in healthy volunteers. The effect of single oral doses (1-2 mg) R137696 was evaluated in a double-blind, placebo-controlled manner on fasting fundic volume, visceral perception, distension-evoked symptoms and fundic compliance in 21 healthy male subjects. R137696 increased the proximal stomach volumes in a dose-dependent manner. Distention-evoked symptoms or distention and discomfort threshold were not altered by R137696. A logistic regression model, characterizing the relationships between the volume and the visual analogue scale score for dyspeptic symptoms (nausea, fullness, discomfort, pain and satiety) as a sigmoidal curve, revealed that R137696 had no effect on distension-induced discomfort, fullness, pain and satiety compared to placebo. R137696 relaxes the gastric fundus in fasting conditions but has no effect on distension-evoked dyspeptic symptoms in healthy volunteers.
Boeckxstaens
G E
GE
Division of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands. g.e.boeckxstaens@amc.uva.nl
Tytgat
G N
GN
Wajs
E
E
van Nueten
L
L
de Ridder
F
F
Meulemans
A
A
Tack
J
J
D000328:Adult; D003187:Compliance / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008365:Manometry; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010147:Pain Measurement; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*
D017366:Serotonin Receptor Agonists