title: Effects of Silodosin, an α1A-Adrenoceptor Antagonist, and Distigmine, an Acetylcholinesterase Inhibitor, and Their Combined Effects on Impaired Voiding Function in Zucker Diabetic Fatty Rats.
abstract: OBJECTIVE
  To evaluate the effects of silodosin (α1A-adrenoceptor antagonist) and distigmine (acetylcholinesterase inhibitor), alone or in combination, on voiding dysfunction in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model, by pressure flow study.
  
  
  METHODS
  Male ZDF rats were anesthetized with urethane and a catheter was implanted into the bladder through the dome. Saline was continuously infused into the bladder at 6 ml/h to induce the micturition reflex. Intravesical pressure and micturition volume were recorded continuously and various urodynamic parameters were calculated using a waveform analysis system.
  
  
  RESULTS
  Increased bladder capacity, residual volume, and urethral resistance and decreased maximum detrusor contraction velocity and urine flow rate, considered to be detrusor underactivity-like symptoms, were observed in ZDF rats. Although both silodosin and distigmine improved impaired voiding function, administration of both drugs in combination was more effective than either drug alone.
  
  
  CONCLUSIONS
  ZDF rats showed symptoms suggestive of detrusor underactivity, and silodosin tended to ameliorate these symptoms in ZDF rats. These results suggested that an α1A-adrenoceptor antagonists may be effective against the voiding disorder accompanying not only bladder outlet obstruction but also deficiency of bladder function. Moreover, combined administration of an α1A-adrenoceptor antagonist with an acetylcholinesterase inhibitor may have additive efficacy in clinical use.
authors.affiliation: Pharmacology Research, R&D, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tatemichi
authors.forename: Kumi
authors.initials: K
authors.lastname: Tsuchioka
authors.forename: Saori
authors.initials: S
authors.lastname: Yonekubo
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Maruyama
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D011924:Rats, Zucker; D014554:Urination / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002800:Cholinesterase Inhibitors; D007211:Indoles; D011726:Pyridinium Compounds; C095285:silodosin; C084645:distigmine