The influence of the novel 5‐HT_1A agonist R137696 on the proximal stomach function in healthy volunteers

Abstract

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.

Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population

“…On the other hand, Tack et al reported that a 5HT1A agonist failed to improve symptoms, visceral hypersensitivity, or gastric accommodation compared with placebo [42]. Boeckxstaens et al also reported that a 5HT1A agonist had no effect on gastric fundus distension-evoked dyspeptic symptoms in healthy volunteers [43]. Talley et al reported that alosetron, a 5HT3 antagonist, had potential benefit in relieving functional dyspepsia symptoms compared to placebo [44].…”

Impaired gastric accommodation and its role in dyspepsia

“…A newly developed 5-HT 1A receptor agonist R-137696 was shown to dose-dependently induce relaxation of the proximal stomach in humans. 92 A subsequent small placebo-controlled 4-week multicentre study failed to show any effect of the drug on gastric compliance and accommodation, suggesting that desensitisation to the drug effect had occurred within this time frame. 93 Presynaptic a 2 receptors are present on intrinsic cholinergic nerve endings in the stomach.…”

The role of serotonin in irritable bowel syndrome: Implications for management

“…Anticholinergic drugs have long been a mainstay for treatment of crampy abdominal pain in patients with a variety of gastrointestinal problems, including IBS. Drugs such as buspirone, sumatriptan, and R137696 [ 35 ], which act on 5-HT1A receptors, may prove effi cacious in treating specifi c symptoms associated with functional bowel disorders.…”