The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome.
OBJECTIVE
Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid kappa 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, a potent and selective kappa 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.
Delvaux
M
M
Laboratory of Digestive Motility, Gastroenterology Unit, Centre Hospitalier Universitaire Rangueil, Toulouse, France. 016521.3337@compuserve.com
Louvel
D
D
Lagier
E
E
Scherrer
B
B
Abitbol
J L
JL
Frexinos
J
J
D000328:Adult; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003109:Colonic Diseases, Functional / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004435:Eating; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008365:Manometry; D008875:Middle Aged; D017288:Pain Threshold / Q000187:drug effects; D011437:Propylamines / Q000008:administration & dosage / Q000627:therapeutic use*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012684:Sensory Thresholds / Q000187:drug effects
D001593:Benzyl Compounds; D011437:Propylamines; D017473:Receptors, Opioid, kappa; C067749:fedotozine