Alimentary TractThe κ agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome☆,☆☆
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 Four additional patients were withdrawn after randomization because the colonic probe did not stay in the left colon during the whole study.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)
- et al.
Effect of anger on colon motor and myoelectric activity in the irritable bowel syndrome
Gastroenterology
(1988) - et al.
Site of pain from the irritable bowel
Lancet
(1980) - et al.
Tolerance for rectosigmoid distension in irritable bowel syndrome
Gastroenterology
(1990) - et al.
Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations
Gastroenterology
(1997) - et al.
Fedotozine reverses ileus induced by surgery or peritonitis. Action at peripheral kappa opioid receptors
Gastroenterology
(1993) - et al.
Peripheral kappa-opioid receptors mediate the antinociceptive effect of fedotozine on the duodenal pain reflex in rat
Eur J Pharmacol
(1994) - et al.
Effect of fedotozine on the cardiovascular pain reflex induced by distension of the irritated colon in the anesthetized rat
Eur J Pharmacol
(1994) - et al.
Distension protocols for evaluation of rectal sensitivity: the simplest, the best
Gastroenterology
(1998) - et al.
Altered rectal perception is a biological marker of patients with irritable bowel syndrome
Gastroenterology
(1995) - et al.
Fedotozine blocks hypersensitive visceral pain in conscious rats: action at peripheral kappa-opioid receptors
Eur J Pharmacol
(1997)
Evaluation of colonic myoelectric activity in health and in functional disorders
Gut
Colonic myoelectrical activity in IBS painless diarrhoea
Gut
Irritable bowel syndrome: physiological and psychological difference between diarrhoea-predominant and constipation-predominant patients
Dig Dis Sci
Motility disorders and stress
Dig Dis Sci
Colonic myoelectrical activity in irritable bowel syndrome. Effect of eating and anticholinergics
N Engl J Med
Postprandial colonic transit and motor activity in chronic constipation
Gastroenterology
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.