title: Pharmacological effects of propiverine and its active metabolite, M-1, on isolated human urinary bladder smooth muscle, and on bladder contraction in rats.
abstract: OBJECTIVE
  To investigate the effects of M-1, a major active metabolite of propiverine on the bladder.
  
  
  METHODS
  We have evaluated the effects of M-1 on the contractions induced by carbachol, KCl, CaCl(2), and electrical field stimulation (EFS) in human detrusor smooth muscles, and pelvic nerve stimulation-induced bladder contractions in rats. The effects of M-1 were also compared with the effects of propiverine and tolterodine.
  
  
  RESULTS
  Pretreatment with propiverine and tolterodine caused parallel shifts to the right of the concentration-response curves to carbachol. M-1 caused concentration-dependent reduction in the maximum contractile responses induced by carbachol. Although tolterodine did not inhibit the KCl- and CaCl(2)-induced contractions, M-1 and propiverine significantly inhibited these contractions. In the presence of atropine, M-1 and propiverine significantly inhibited the atropine resistant part of the contraction induced by EFS. On the other hand, tolterodine did not have significant inhibitory effects on atropine resistant contractions. Pelvic nerve stimulation induced bimodal phasic and tonic contractions in the rat bladder. M-1 mainly inhibited the phasic contraction. Tolterodine caused a significant inhibition in the tonic contraction, and propiverine had inhibitory effects on both contractions.
  
  
  CONCLUSIONS
  The present results suggest that M-1 has inhibitory effects on the bladder smooth muscles through calcium antagonistic action. It is possible that the clinical effects of propiverine on the human bladder are based not only on the action of propiverine itself but also on one of its active metabolites, M-1.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Koichi
authors.initials: K
authors.lastname: Masunaga
authors.forename: You
authors.initials: Y
authors.lastname: Satoji
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagata
authors.forename: Akito
authors.initials: A
authors.lastname: Inadome
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ueda
mesh_terms: D000368:Aged; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001561:Benzilates / Q000494:pharmacology*; D002217:Carbachol; D018679:Cholinergic Agonists; D003408:Cresols / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D006801:Humans; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010665:Phenylpropanolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000187:drug effects*
chemical_list: D001559:Benzhydryl Compounds; D001561:Benzilates; D018679:Cholinergic Agonists; D003408:Cresols; D003497:Cyclic N-Oxides; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; C113811:propiverine N-oxide; D010665:Phenylpropanolamine; C015586:propiverine; D000068737:Tolterodine Tartrate; D002217:Carbachol