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 (p
Ki 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.
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