Zamifenacin (UK-76, 654), a potent gut M₃ selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

Background: Zamifenacin is a new potent gut M₃ selective muscarinic antagonist developed for possible use in irritable bowel syndrome. Methods: In this multicentre, double-blind, parallel group, placebo-controlled 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 assessed in 36 patients with irritable bowel syndrome (aged 25-68 years: 19 male). Colonic motility was recorded using a five-channel solid-state catheter introduced by colonoscopy to a depth of 35 cm in an unprepared colon. Results: Zamifenacin 40 mg profoundly reduced colonic motility, 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 and the motility index (P < 0.05). A smaller reduction in all the motility 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 colonic motility in irritable bowel syndrome patients without significant antimuscarinic effects. The results of this study confirm that the concept of developing selective antimuscarinic agents may be a promising approach to the treatment of irritable bowel syndrome. Not only would such compounds benefit from not having the usual side-effects of anticholinergics but they might also offer much more in the way of dose flexibility.