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标题：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
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作者：Shuichi Sato ; Toshiki Hatanaka ; Hironori Yuyama 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2012
卷号：35
期号：1
页码：72-77
DOI：10.1248/bpb.35.72
出版社：The Pharmaceutical Society of Japan
摘要：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 α_1A-, α_1B- and α_1D-adrenoceptors (p K _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.
关键词：[3H]tamsulosin;α1A-adrenoceptor;dissociation rate;α1-adrenoceptor antagonist