The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome

Background & Aims: Visceral hypersensitivity plays a major role in the path ophysiology of inflammatory bower syndrome (IBS). Opioid kappa receptors on afferent nerves may modulate it and may be the target of new IBS treatment s. The aim of this study was to evaluate the effects of fedotozine, a poten t and selective kappa agonist, on responses to colonic distention and colon ic compliance in patients with IBS. Methods: Fourteen patients with IBS (Ro me criteria; 50 +/- 12 years; 6 men and 8 women) were included in a randomi zed doubleblind, crossover trial comparing the effect of an intravenous inf usion 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 pressu re-volume curves built on placebo and on fedotozine. Results: In the fedoto zine group, thresholds of first perception (28.7 +/- 5.9 mm Hg) and pain (3 4.7 +/- 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 wa s 9.20 +/- 3.87 mL.mm Hg-1 with placebo and 8.73 +/- 3.18 mL.mm Hg-1 with f edotozine (not significant). Conclusions: Fedotozine increases thresholds o f perception of colonic distention in patients with IBS without modifying c olonic compliance. Fedotozine seems capable of reversing visceral hypersens itivity observed in these patients and could have some beneficial action on their symptoms.