Gastroenterology

Gastroenterology

Volume 116, Issue 1, January 1999, Pages 38-45
Gastroenterology

Alimentary Tract
The κ agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome,☆☆

https://doi.org/10.1016/S0016-5085(99)70226-XGet rights and content

Abstract

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, 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

Section snippets

Patients

The study was divided into two parts. Part one was designed to evaluate sensory thresholds elicited by colonic distention. Twelve patients were to be included in this part of the study. Six additional patients were to be studied in part two, which evaluated the effect of fedotozine on fasting and postprandial colonic tone.

All patients had a clinical diagnosis of IBS based on Rome criteria.24 Patients gave informed consent to participate in the experimental procedures approved by the Regional

Tolerance of the treatment, probe, and technical aspects of recording sessions

Thirty patients were screened for completion of both parts of this study. Twenty-four of them were expected to participate in the first part of the study, evaluating sensory thresholds and the effect of fedotozine on them. After the first attempt of colonic distention was performed, 6 patients were excluded because they had a pain threshold of >32 mm Hg. Four additional patients were withdrawn after randomization because the colonic probe did not stay in the left colon during the whole study.

Discussion

In this study we show that fedotozine, a κ opioid receptors agonist, is able to relieve the hypersensitivity characterizing patients with painful IBS, whereas it does not alter colonic compliance and does not modify the characteristics of tonic response of the left colon to eating.

All experimental procedures were based on a double-blind, randomized, crossover protocol using a continuous intravenous infusion of fedotozine or placebo, resulting in stable plasma levels of fedotozine at the time

Acknowledgements

The authors thank Marcel Caussette and Thierry Hachet for providing the probes and maintaining the barostat and the nurses at the Clinical Unit of Gastroenterology for surveillance recordings.

References (33)

  • L Buéno et al.

    Evaluation of colonic myoelectric activity in health and in functional disorders

    Gut

    (1985)
  • J Frexinos et al.

    Colonic myoelectrical activity in IBS painless diarrhoea

    Gut

    (1987)
  • WE Whitehead et al.

    Irritable bowel syndrome: physiological and psychological difference between diarrhoea-predominant and constipation-predominant patients

    Dig Dis Sci

    (1980)
  • M Camilleri et al.

    Motility disorders and stress

    Dig Dis Sci

    (1989)
  • MA Sullivan et al.

    Colonic myoelectrical activity in irritable bowel syndrome. Effect of eating and anticholinergics

    N Engl J Med

    (1978)
  • G Bazzochi et al.

    Postprandial colonic transit and motor activity in chronic constipation

    Gastroenterology

    (1990)
  • Cited by (0)

    Supported by a grant from the Jouveinal Research Institute, Paris, France.

    ☆☆

    Address requests for reprints to: Michel Delvaux, M.D., Ph.D., Gastroenterology Unit, CHU Rangueil, F-31403, Toulouse Cédex 04, France. e-mail: [email protected]; fax: (33) 561-32-22-29.

    View full text