Taguchi K, Saitoh M, Sato S, Asano M, Michel M C
Department of Medicine, University of Essen, Germany.
J Pharmacol Exp Ther. 1997 Jan;280(1):1-5.
We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin binding to the rat liver and kidney alpha-1 adrenoceptors, with the rank order of potency tamsulosin approximately M4 > M1 > M2 approximately M3 > > AM1 with the latter having a negligible affinity. All compounds differentiated cloned alpha-1 adrenoceptor subtypes with the rank order of potency of alpha-1A > or = alpha-1D > alpha-1B, except for M4 which had the highest affinity for the alpha-1D adrenoceptor. The compounds also concentration-dependently antagonized phenylephrine-induced contractions in the rabbit aorta and prostate. The resulting apparent pA2 values were very similar to those at the cloned rat alpha-1A adrenoceptor. We conclude that most tamsulosin metabolites are high potency antagonists at the alpha-1 adrenoceptors and retain the alpha-1A over the alpha-1B adrenoceptor selectivity of tamsulosin.
我们在放射性配体结合和功能研究中，研究了坦索罗辛及其代谢产物M1、M2、M3、M4和AM1在组织及克隆的α-1肾上腺素能受体亚型上的亲和力和选择性。在放射性配体结合研究中，这些化合物竞争[3H]哌唑嗪与大鼠肝脏和肾脏α-1肾上腺素能受体的结合，效力顺序为坦索罗辛约M4 > M1 > M2约M3 > > AM1，后者的亲和力可忽略不计。除M4对α-1D肾上腺素能受体具有最高亲和力外，所有化合物对克隆的α-1肾上腺素能受体亚型的区分效力顺序为α-1A≥α-1D > α-1B。这些化合物还能浓度依赖性地拮抗苯肾上腺素诱导的兔主动脉和前列腺收缩。所得的表观pA2值与克隆的大鼠α-1A肾上腺素能受体上的值非常相似。我们得出结论，大多数坦索罗辛代谢产物是α-1肾上腺素能受体的高效拮抗剂，并保留了坦索罗辛对α-1A肾上腺素能受体相对于α-1B肾上腺素能受体的选择性。
