The selectivity of silodosin (KMD-3213), an antagonist of α
1-adrenoceptor (AR), to the subtypes (α
1A-, α
1B- and α
1D-ARs) was examined by a receptor-binding study and a functional pharmacological study, and we compared its subtype-selectivity with those of other α
1-AR antagonists. In the receptor-binding study, a replacement experiment using [
3H]-prazosin was conducted using the membrane fraction of mouse-derived LM (tk-) cells in which each of three human α
1-AR subtypes was expressed. In the functional pharmacological study, the following isolated tissues were used as representative organs with high distribution densities of α
1-AR subtypes (α
1A-AR: rabbit prostate, urethra and bladder trigone; α
1B-AR: rat spleen; α
1D-AR: rat thoracic aorta). Using the Magnus method, we studied the inhibitory effect of silodosin on noradrenaline-induced contraction, and compared it with those of tamsulosin hydrochloride, naftopidil and prazosin hydrochloride. Silodosin showed higher selectivity for the α
1A-AR subtype than tamsulosin hydrochloride, naftopidil or prazosin hydrochloride (affinity was highest for tamsulosin hydrochloride, followed by silodosin, prazosin hydrochloride and naftopidil in that order). Silodosin strong antagonized noradrenaline-induced contractions in rabbit lower urinary tract tissues (including prostate, urethra and bladder trigone, with pA
2 or p
Kb values of 9.60, 8.71 and 9.35, respectively). On the other hand, the pA
2 values for antagonism of noradrenaline-induced contractions in rat isolated spleen and rat isolated thoracic aorta were 7.15 and 7.88, respectively. Selectivity for lower urinary tract was higher for silodosin than for the other α
1-AR antagonists. Our data suggest that silodosin has a high selectivity for the α
1A-AR subtype and for the lower urinary tract.
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