Tamsulosin Potently and Selectively Antagonizes Human Recombinant α1A/1D-Adrenoceptors: Slow Dissociation from the α1A-Adrenoceptor May Account for Selectivity for α1A-Adrenoceptor over α1B-Adrenoceptor Subtype

We determined the binding affinity of tamsulosin, a selective aradrenoceptor antagonist, for human aradrenoceptor subtypes in comparison with those of other alpha(1)-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [H-3]tamsulosin for recombinant human alpha(1)-adrenoceptor subtypes were compared with those of [H-3]prazosin. Tamsulosin competitively inhibited [H-3]prazosin binding to human alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptors (pK(i) values were 10.38, 9.33, 9.85) indicating 11 and 3.4-fold higher affinities for human alpha(1A)-adrenoceptor than those for alpha(1B)- and alpha(1D)-adrenoceptors, respectively. The affinity of tamsulosin for the human awadrenoceptor 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. [H-3]Tamsulosin dissociated from the alpha(1A)-adrenoceptor slower than from the alpha(1B)- and alpha(1D)-adrenoceptors (alpha(1B)>alpha(1D)>alpha(1A)). Moreover, [H-3]tamsulosin dissociated slower than [H-3]prazosin from the alpha(1A)-adrenoceptor and faster from the alpha(1B)- and alpha(1D)-adrenoceptors. In conclusion, tamsulosin potently and selectively antagonized alpha(1A/1D)-adrenoceptor ligand binding, and slowly dissociated from the alpha(1A)-adrenoceptor subtype.