Asano M, Hashimoto H, Nakashima M
Arch Int Pharmacodyn Ther. 1983 Mar;262(1):34-46.
The binding properties of YM-09538 and some known adrenoceptor agonists and antagonists to alpha- and beta-adrenoceptors were studied by radioligand binding assays using [3H]-prazosin, [3H]-clonidine and (-)-[3H]-dihydroalprenolol ([3H]-DHA). The relative order of potencies of YM-09538 and 5 alpha-adrenergic agents for inhibition of [3H]-prazosin binding to rat brain membranes was as follows: prazosin greater than YM-09538 = phentolamine greater than labetalol greater than yohimbine greater than clonidine. In contrast, the order of potencies of these agents for [3H]-clonidine sites was as follows: clonidine greater than phentolamine greater than yohimbine greater than prazosin greater than YM-09538 greater than labetalol. The rank order of potencies of YM-09538 and 4 beta-adrenergic agents in inhibiting the binding of [3H]-DHA to guinea-pig heart membranes was the same as that to guinea-pig lung membranes: pindolol greater than propranolol greater than labetalol greater than YM-09538 greater than atenolol. Based on Ki values, YM-09538 displayed a 1,380-fold alpha 1-selectivity at alpha-adrenoceptors and no selectivity at beta-adrenoceptors. The biochemical potencies of YM-09538 observed in the present study correlated well with its pharmacological potencies obtained from previously reported literature.
使用[3H]-哌唑嗪、[3H]-可乐定和(-)-[3H]-二氢烯丙洛尔（[3H]-DHA），通过放射性配体结合试验研究了YM-09538以及一些已知的肾上腺素能受体激动剂和拮抗剂与α和β肾上腺素能受体的结合特性。YM-09538和5种α肾上腺素能药物抑制[3H]-哌唑嗪与大鼠脑膜结合的效价相对顺序如下：哌唑嗪＞YM-09538 = 酚妥拉明＞拉贝洛尔＞育亨宾＞可乐定。相比之下，这些药物作用于[3H]-可乐定位点的效价顺序如下：可乐定＞酚妥拉明＞育亨宾＞哌唑嗪＞YM-09538＞拉贝洛尔。YM-09538和4种β肾上腺素能药物抑制[3H]-DHA与豚鼠心脏膜结合的效价排序与它们抑制[3H]-DHA与豚鼠肺膜结合的效价排序相同：吲哚洛尔＞普萘洛尔＞拉贝洛尔＞YM-09538＞阿替洛尔。基于Ki值，YM-09538在α肾上腺素能受体上表现出1380倍的α1选择性，在β肾上腺素能受体上无选择性。本研究中观察到的YM-09538的生化效价与其从先前报道的文献中获得的药理效价密切相关。
