title: Effect of hyoscine butylbromide (Buscopan®) on cholinergic pathways in the human intestine.
abstract: BACKGROUND
  Hyoscine butylbromide (HBB, Buscopan(®) ) is clinically used to treat intestinal cramps and visceral pain. Various studies, mainly on animal tissues, suggested that its antimuscarinic action is responsible for its spasmolytic effect. However, functional in vitro studies with human tissue have not been performed so far.
  
  
  METHODS
  We wanted to provide a comprehensive study on the mode of action of HBB in human intestinal samples and investigated HBB (1 nmol L(-1) -10 μmol L(-1)) effects on muscle activity with isometric force transducers and calcium imaging, on epithelial secretion with Ussing chamber technique and on enteric neurons using fast neuroimaging.
  
  
  RESULTS
  Hyoscine butylbromide concentration dependently reduced muscle contractions, calcium mobilization, and epithelial secretion induced by the muscarinic agonist bethanechol with IC50 values of 429, 121, and 224 nmol L(-1), respectively. Forskolin-induced secretion was not altered by HBB. Cholinergic muscarinic muscle and epithelial responses evoked by electrical nerve stimulation were inhibited by 1-10 μmol L(-1) HBB. Moreover, HBB significantly reduced the bethanechol-induced action potential discharge in enteric neurons. Interestingly, we observed that high concentrations of HBB (10 μmol L(-1)) moderately decreased nicotinic receptor-mediated secretion, motility, and nerve activity.
  
  
  CONCLUSIONS
  The results demonstrated the strong antimuscarinic action of HBB whereas the nicotinic antagonism at higher concentrations plays at most a moderate modulatory role. The muscle relaxing effect of HBB and its inhibition of muscarinic nerve activation likely explain its clinical use as an antispasmodic drug. Our results further highlight a so far unknown antisecretory action of HBB which warrants further clinical studies on its use in secretory disorders.
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Krueger
authors.forename: K
authors.initials: K
authors.lastname: Michel
authors.forename: S
authors.initials: S
authors.lastname: Allam
authors.forename: T
authors.initials: T
authors.lastname: Weiser
authors.forename: I E
authors.initials: IE
authors.lastname: Demir
authors.forename: G O
authors.initials: GO
authors.lastname: Ceyhan
authors.forename: F
authors.initials: F
authors.lastname: Zeller
authors.forename: M
authors.initials: M
authors.lastname: Schemann
mesh_terms: D002086:Butylscopolammonium Bromide / Q000494:pharmacology*; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D007422:Intestines / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques
chemical_list: D018727:Muscarinic Antagonists; D002086:Butylscopolammonium Bromide
keywords: enteric nervous system; epithelial secretion; hyoscine butylbromide; muscarinic receptor; smooth muscle motility