Effects of silodosin and naftopidil on the distal ureter and cardiovascular system in anesthetized dogs: comparison of potential medications for distal ureteral stone passage.
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.
Kobayashi
Shinya
S
Pharmacology Research and Development, Kissei Pharmaceutical Co Ltd, Nagano, Aichi, Japan. shinya_kobayashi@pharm.kissei.co.jp
Tomiyama
Yoshitaka
Y
Hoyano
Yuji
Y
Yamazaki
Yoshinobu
Y
Sasaki
Shoichi
S
Kohri
Kenjiro
K
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*
D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D009281:Naphthalenes; D010879:Piperazines; C095285:silodosin; C064357:naftopidil