The selectivity of silodosin , an antagonist of a 1 -adrenoceptor (AR), to the subtypes (a 1A -, a 1B -and a 1D -ARs) was examined by a receptor-binding study and a functional pharmacological study, and we compared its subtype-selectivity with those of other a 1 -AR antagonists. In the receptor-binding study, a replacement experiment using [ 3 H]-prazosin was conducted using the membrane fraction of mouse-derived LM (tk-) cells in which each of three human a 1 -AR subtypes was expressed. In the functional pharmacological study, the following isolated tissues were used as representative organs with high distribution densities of a 1 -AR subtypes (a 1A -AR: rabbit prostate, urethra and bladder trigone; a 1B -AR: rat spleen; a 1D -AR: rat thoracic aorta). Using the Magnus method, we studied the inhibitory eŠect of silodosin on noradrenaline-induced contraction, and compared it with those of tamsulosin hydrochloride, naftopidil and prazosin hydrochloride. Silodosin showed higher selectivity for the a 1A -AR subtype than tamsulosin hydrochloride, naftopidil or prazosin hydrochloride (a‹nity 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 pKb 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 a 1 -AR antagonists. Our data suggest that silodosin has a high selectivity for the a 1A -AR subtype and for the lower urinary tract.Key words-silodosin (KMD-3213); a 1A -adrenoceptor subtype selectivity; lower urinary tract

The selectivity of silodosin (KMD − 3213)， an antagonist of or1− adrenoceptor (AR) ， to the subtypes (α 且 A − ， α IB − and α ID − ARs)was examined by a receptor − binding study and a functional pharmacological study ， and we compared its sub − type − selectivity With those of other α 1 − AR antagonjsts ． 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 hu − man ai − AR subtypes was expressed ． ln 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 methQd ， we studied the inhibitory effect of silodosin on noradrenalille − 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(aMnity 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 trigon ¢ ， with pA20r pKb values of 9 ． 60， 8． 71 and 9． 35， respectively) 。 On the other hand ， the pA2 values for antagonism of noradrenaline ． induced contractions in rat iso − 1ated spleen and rat isolated thoracic aorta were 7 ． 15and 7 ， 88 ， respectively ． Seiectivity 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 ．

Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients.

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