Effects of four different alpha(1)-adrenoceptor antagonists on alpha-adrenoceptor agonist-induced contractions in isolated mouse and hamster ureters.
OBJECTIVE
To compare the efficacy of the selective alpha(1A)-adrenoceptor antagonist silodosin with those of doxazosin, terazosin, and alfuzosin against alpha-adrenoceptor agonist-induced contractions in mouse and hamster ureters.


METHODS
The four alpha(1)-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique.


RESULTS
In mouse ureters, silodosin (a selective alpha(1A)-adrenoceptor antagonist), doxazosin (a nonselective alpha(1)-adrenoceptor antagonist), terazosin (a nonselective alpha(1)-adrenoceptor antagonist), and alfuzosin (a nonselective alpha(1)-adrenoceptor antagonist) all shifted the norepinephrine concentration-response curve to the right. The rank order of potencies (pK(B) value) was silodosin (9.47 +/- 0.16) > doxazosin (8.62 +/- 0.15) > terazosin (8.39 +/- 0.16) > alfuzosin (8.03 +/- 0.12). In hamster ureters, all four antagonists shifted the phenylephrine concentration-response curve to the right, the rank order of potencies being silodosin (10.09 +/- 0.13) > doxazosin (8.22 +/- 0.16) > terazosin (7.75 +/- 0.15) > alfuzosin (7.70 +/- 0.10). In each case, silodosin was much more potent than the other three drugs.


CONCLUSIONS
In this study, silodosin suppressed both mouse and hamster ureteral contractions more potently than doxazosin, terazosin, or alfuzosin. Hence, this alpha(1A)-adrenoceptor antagonist warrants further study as a potentially very useful medication for stone passage in urolithiasis patients.
Pharmacology, Research and Development, Kissei Pharmaceutical Co. Ltd., Azumino, Nagano, Japan. shinya_kobayashi@pharm.kissei.co.jp
Shinya
S
Kobayashi
Yoshitaka
Y
Tomiyama
Kazuyasu
K
Maruyama
Yuji
Y
Hoyano
Yoshinobu
Y
Yamazaki
Hiroshi
H
Kusama
D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D017292:Doxazosin / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D014513:Ureter / Q000187:drug effects* / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D011799:Quinazolines; C041226:Terazosin; C047638:alfuzosin; C095285:silodosin; D017292:Doxazosin; D009638:Norepinephrine; D011224:Prazosin