title: Zamifenacin (UK-76, 654) a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University Hospital of South Manchester, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Houghton
authors.forename: J
authors.initials: J
authors.lastname: Rogers
authors.forename: P J
authors.initials: PJ
authors.lastname: Whorwell
authors.forename: F C
authors.initials: FC
authors.lastname: Campbell
authors.forename: N S
authors.initials: NS
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Goka
mesh_terms: D000328:Adult; D000368:Aged; D003109:Colonic Diseases, Functional / Q000188:drug therapy*; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D004149:Dioxoles; D018727:Muscarinic Antagonists; D010880:Piperidines; C097932:zamifenacin