ZAMIFENACIN (UK-76, 654), A POTENT GUT M-3 SELECTIVE MUSCARINIC ANTAGONIST, REDUCES COLONIC MOTOR-ACTIVITY IN PATIENTS WITH IRRITABLE-BOWEL-SYNDROME

Background: Zamifenacin is a new potent gut M-3 selective muscarinic a ntagonist developed for possible use in irritable bowel syndrome. Meth ods: In this multicentre, double-blind, parallel group, placebo-contro lled study, the effect of a single dose of zamifenacin 10 mg or 40 mg on both fasting (30 min) and fed (60 min) colonic motor activity was a ssessed in 36 patients with irritable bowel syndrome (aged 25-68 years ; 19 male). Colonic motility was recorded using a five-channel solid-s tate catheter introduced by colonoscopy to a depth of 35 cm in an unpr epared colon. Results: Zamifenacin 40 mg profoundly reduced colonic mo tility, particularly after the meal (P < 0.05). This was reflected by a significant reduction in the mean amplitude of contractions, number of contractions, percentage duration of contractions, activity index a nd the motility index (P < 0.05). A smaller reduction in all the motil ity parameters was obtained with 10 mg zamifenacin, but these changes were not statistically significant. Three patients each on placebo and zamifenacin reported side-effects, but these were mild and transient. Conclusion: A single 40 mg dose of zamifenacin significantly reduces c olonic motility in irritable bowel syndrome patients without significa nt antimuscarinic effects, The results of this study confirm that the concept of developing selective antimuscarinic agents may be a promisi ng approach to the treatment of irritable bowel syndrome. Not only wou ld such compounds benefit from not having the usual side-effects of an ticholinergics but they might also offer much more in the way of dose flexibility.