title: Synergic Suppressive Effect of Silodosin and Imidafenacin on Non-Voiding Bladder Contractions in Male Rats with Subacute Bladder Outlet Obstruction.
abstract: OBJECTIVE
  To investigate single or combined effect of silodosin, an α1A-adrenoceptor antagonist, and imidafenacin, an antimuscarinic agent, on bladder function in a subacute bladder outlet obstruction (BOO) model of male rats.
  
  
  METHODS
  Partial BOO was created in male Wistar rats by ligating the urethra with a steel rod. On day 10 after surgery, when frequent voiding was most remarkable on voiding behavior measurement in a metabolic cage, cystometric investigations in a conscious restrained condition were conducted with cumulative intravenous administration of silodosin alone (0.1, 1, 10, and 100 µg/kg), imidafenacin alone (1, 3, and 10 µg/kg), or a combination of the two drugs.
  
  
  RESULTS
  When compared with the Sham rats, the BOO rats showed an increase in bladder capacity, residual volume, mean amplitude and the number of non-voiding contractions (NVCs), accompanied with an increase in bladder weight. In the BOO rats, silodosin alone at 100 µg/kg significantly decreased the number of NVCs, whereas imidafenacin alone at 3 and 10 µg/kg significantly decreased both the number and mean amplitude of NVCs. The combination administration with lower doses (silodosin at 10 µg/kg and imidafenacin at 1 µg/kg) significantly suppressed both the number and mean amplitude of NVCs.
  
  
  CONCLUSIONS
  The present results indicate a suppressive effect of silodosin or imidafenacin alone and a synergic effect of the combination of these two drugs on NVCs in a subacute BOO model of male rats.
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.|Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Rino
authors.initials: R
authors.lastname: Sugiyama
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aizawa
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004338:Drug Combinations; D007093:Imidazoles / Q000493:pharmacokinetics*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009929:Organ Size; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000473:pathology; D014554:Urination / Q000187:drug effects; D064804:Urological Agents / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D007093:Imidazoles; D007211:Indoles; D018727:Muscarinic Antagonists; D064804:Urological Agents; C095285:silodosin; C120953:imidafenacin
keywords: Wistar rats; adrenergic alpha-1 receptor antagonists; bladder outlet obstruction; muscarinic antagonists; urinary bladder