title: Effects of silodosin and naftopidil on the distal ureter and cardiovascular system in anesthetized dogs: comparison of potential medications for distal ureteral stone passage.
abstract: OBJECTIVE
  We compared the effects of the selective alpha(1A)-adrenoceptor antagonist silodosin and the selective alpha(1D)-adrenoceptor antagonist naftopidil on intraureteral pressure in anesthetized dogs and evaluated their uroselectivity.
  
  
  METHODS
  Using anesthesia the effects of silodosin and naftopidil were evaluated by the phenylephrine induced increase in intravesical ureteral pressure and on blood pressure. Each drug was administered intravenously in progressively increasing doses. The dose of each alpha(1)-adrenoceptor antagonist at which mean blood pressure was decreased by 15% (ED(15)) and the dose at which the phenylephrine induced increase in intravesical ureteral pressure was suppressed by 50% (ID(50)) were measured and uroselectivity was calculated as ED(15)/ID(50).
  
  
  RESULTS
  Silodosin dose dependently suppressed the phenylephrine induced increase in intravesical ureteral pressure (ID(50) 2.5 microg/kg) but decreased mean blood pressure only at higher doses (ED(15) 143.4 microg/kg). In contrast, naftopidil decreased mean blood pressure (ED(15) 280.7 microg/kg) at the same doses as those that decreased the phenylephrine induced increase in intravesical ureteral pressure (ID(50) 225.1 microg/kg). Silodosin uroselectivity was markedly higher than that of naftopidil (58.6 vs 1.3).
  
  
  CONCLUSIONS
  Results suggest that a selective alpha(1A)-adrenoceptor antagonist such as silodosin may facilitate distal ureteral stone passage at nonhypotensive doses.
authors.affiliation: Pharmacology Research and Development, Kissei Pharmaceutical Co Ltd, Nagano, Aichi, Japan. shinya_kobayashi@pharm.kissei.co.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hoyano
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000758:Anesthesia; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D014513:Ureter / Q000187:drug effects*; D014514:Ureteral Calculi / Q000188:drug therapy*
chemical_list: D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D009281:Naphthalenes; D010879:Piperazines; C095285:silodosin; C064357:naftopidil