Double blind placebo controlled study on the effect of the nitric oxide donor molsidomin and the 5-HT3 antagonist ondansetron on human esophageal motility.
The aim of the present study was to investigate the effects of acute administration of the NO-donor molsidomin (2 mg) and the 5-HT3 antagonist ondansetron (8 mg) on esophageal motility and lower esophageal sphincter pressure (LESP) in 10 healthy volunteers by stationary side hole manometry in a double-blind placebo controlled study design. LESP, contraction amplitudes (5, 10, 15 cm above the LES) and propagation velocity (10-15 cm above the LES) for dry and wet swallows were analysed and additional blood samples were taken for determination of plasma levels of VIP and gastrin. Molsidomin significantly decreased basal LESP from 16.8 +/- 1.6 mmHg to 11.4 +/- 1.0 mmHg, while ondansetron had no influence. Molsidomin also reduced contraction amplitudes of dry swallows (saline 61.9 +/- 7.2 mmHg, molsidomin 40.1 +/- 8.1 mmHg), while it did not influence contraction amplitudes of wet swallows. Ondansetron had no effect on contraction amplitudes. Both substances did not influence propagation velocity of wet swallows, while they reduced propagation velocity of dry swallows significantly (saline 3.9 +/- 0.4 cmls, ondansetron 3.1 +/- 0.2 cm/s, molsidomin 3.1 +/- 0.2 cmls). There were no effects on plasma levels of gastrin or VIP. These data strongly suggest a possible therapeutic role of molsidomin in the treatment of esophageal motility disorders. Effects of ondansetron have to be further evaluated in patients with disturbed esophageal motility.
Willis
S
S
Department of Surgery, Rhenish Westphalian Technical University, Aacher, Germany.
Allescher
H D
HD
Stoschus
B
B
Schusdziarra
V
V
Classen
M
M
Schumpelick
V
V
D000328:Adult; D003679:Deglutition / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005755:Gastrins / Q000097:blood; D006801:Humans; D008297:Male; D008365:Manometry; D008981:Molsidomine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D017294:Ondansetron / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists; D014660:Vasoactive Intestinal Peptide / Q000097:blood
D005755:Gastrins; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D017294:Ondansetron; D008981:Molsidomine