Add time:08/08/2019         Source:sciencedirect.com

Background & Aims: Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid κ receptors on afferent nerves may modulate it and may be the target of new IBS treatments. The aim of this study was to evaluate the effects of fedotozine (cas 123618-00-8), a potent and selective κ agonist, on responses to colonic distention and colonic compliance in patients with IBS. Methods: Fourteen patients with IBS (Rome criteria; 50 ± 12 years; 6 men and 8 women) were included in a randomized double-blind, crossover trial comparing the effect of an intravenous infusion of 100 mg fedotozine or saline on sensory thresholds elicited by left colon phasic distention (4–mm Hg steps for 5 minutes) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure-volume curves built on placebo and on fedotozine. Results: In the fedotozine group, thresholds of first perception (28.7 ± 5.9 mm Hg) and pain (34.7 ± 5.5 mm Hg) were significantly greater than with placebo (23.3 ± 4.5 and 29.0 ± 3.5 mm Hg, respectively; P = 0.0078). Colonic compliance was 9.20 ± 3.87 mL · mm Hg−1 with placebo and 8.73 ± 3.18 mL · mm Hg−1 with fedotozine (not significant). Conclusions: Fedotozine increases thresholds of perception of colonic distention in patients with IBS without modifying colonic compliance. Fedotozine seems capable of reversing visceral hypersensitivity observed in these patients and could have some beneficial action on their symptoms.GASTROENTEROLOGY 1999;116:38-45

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