title: Modulation of Bladder Afferent Activity by Propiverine and its Active Metabolites (M-1 and M-2) in Rats.
abstract: OBJECTIVE
  To evaluate the effects of propiverine and its active metabolites (M-1 and M-2) on bladder function through modulation of afferent activity in rats.
  
  
  METHODS
  Cystometry was performed in urethane anesthetized female rats. We examined the effects of intravesical administration of propiverine, M-1 and M-2 on bladder overactivity induced by oxotremorine-M (Oxo-M; non-selective mAChR agonist).
  
  
  RESULTS
  Intravesical administration of Oxo-M (200 µM) elicited bladder overactivity as evidenced by decreased intercontraction interval (ICI) and pressure threshold (PT) without changing maximum voiding pressure or baseline pressure. These effects were blocked by intravesical administration of propiverine (30 µM) or M-2 (300 µM). Intravesical administration of M-1 (30 µM) alone increased ICI and PT, but did not prevent Oxo-M-induced decreases in ICI and PT.
  
  
  CONCLUSIONS
  These results suggest that propiverine and M-2 have anticholinergic effects on bladder afferent activity and that M-1 has an inhibitory effect through the mechanism other than muscarinic receptor modulation. Thus, clinical benefits of propiverine in patients with overactive bladder could be mediated by multiple actions of propiverine and its active metabolites.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Torimoto
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nanri
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kiniwa
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Urology, Nara Medical University, Nara, JapanTaiho Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
keywords: afferent pathway; metabolite; propiverine; rat; urinary bladder