Tamsulosin Potently and Selectively Antagonizes Human Recombinant .ALPHA.1A/1D-Adrenoceptors: Slow Dissociation from the .ALPHA.1A-Adrenoceptor May Account for Selectivity for .ALPHA.1A-Adrenoceptor over .ALPHA.1B-Adrenoceptor Subtype

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We determined the binding affinity of tamsulosin, a selective α1-adrenoceptor antagonist, for human α1-adrenoceptor subtypes in comparison with those of other α1-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [3H]tamsulosin for recombinant human α1-adrenoceptor subtypes were compared with those of [3H]prazosin. Tamsulosin competitively inhibited [3H]prazosin binding to human α1A-, α1B- and α1D-adrenoceptors (pKi values were 10.38, 9.33, 9.85) indicating 11 and 3.4-fold higher affinities for human α1A-adrenoceptor than those for α1B- and α1D-adrenoceptors, respectively. The affinity of tamsulosin for the human α1A-adrenoceptor was, respectively, 5, 9.9, 38, 120, 280, 400, 1200 and 10000 fold higher than those of silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, naftopidil, urapidil and BMY7378, respectively. [3H]Tamsulosin dissociated from the α1A-adrenoceptor slower than from the α1B- and α1D-adrenoceptors (α1B>α1D>α1A). Moreover, [3H]tamsulosin dissociated slower than [3H]prazosin from the α1A-adrenoceptor and faster from the α1B- and α1D-adrenoceptors. In conclusion, tamsulosin potently and selectively antagonized α1A/1D-adrenoceptor ligand binding, and slowly dissociated from the α1A-adrenoceptor subtype.