Tamsulosin potently and selectively antagonizes human recombinant α 1A/1D-adrenoceptors: Slow dissociation from the α 1A-adrenoceptor May account for selectivity for α 1A-adrenoceptor over α 1B-adrenoceptor subtype

Abstract

We determined the binding affinity of tamsulosin, a selective α 1-adrenoceptor antagonist, for human α 1- adrenoceptor subtypes in comparison with those of other α 1- adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [ 3H]tamsulosin for recombinant human α 1-adrenoceptor subtypes were compared with those of [ 3H]prazosin. Tamsulosin competitively inhibited [ 3H] prazosin binding to human α 1A-, α 1B- and α 1D-adrenoceptors (pK i values were 10.38, 9.33, 9.85) indicating 11 and 3.4-fold higher affinities for human α 1A-adrenoceptor than those for α 1B- and α 1D-adrenoceptors, respectively. The affinity of tamsulosin for the human α 1A-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 α 1A-adrenoceptor slower than from the α 1B- and α 1D-adrenoceptors (α 1B>α 1D>α 1A). Moreover, [ 3H]tamsulosin dissociated slower than [ 3H]prazosin from the α 1A- adrenoceptor and faster from the α 1B- and α 1D- adrenoceptors. In conclusion, tamsulosin potently and selectively antagonized α 1A/1D-adrenoceptor ligand binding, and slowly dissociated from the α 1A-adrenoceptor subtype. © 2012 The Pharmaceutical Society of Japan.