Ishii A, Nishida K, Oka T, Nakamizo N
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Arzneimittelforschung. 1988 Nov;38(11A):1681-3.
The dissociation rates of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) and some calcium antagonists from 3H-nitrendipine binding sites were studied by a centrifugation technique and a filter-absorbed tissue method. KW-3049 dissociated from 3H-nitrendipine binding sites more slowly than other calcium antagonist, namely nifedipine, nitrendipine, nilvadipine, nicardipine and nisoldipine. The slow dissociation of KW-3049 from 3H-nitrendipine binding sites was supported by the equilibrium binding studies. When KW-3049 was preincubated with rat cardiac membrane, its inhibitory potency was enhanced 2.6-fold, whereas nifedipine did not alter its potency. In ex vivo binding, following administration of KW-3049 to rat, 3H-nitrendipine binding site was occupied in a dose-dependent manner and this occupation returned to a control level after 24 h. These results of receptor binding studies are in agreement with the pharmacological characteristics of KW-3049.
采用离心技术和滤膜吸附组织法，研究了（±）-（R*）-2,6-二甲基-4-（间硝基苯基）-1,4-二氢吡啶-3,5-二羧酸（R*）-1-苄基-3-哌啶酯甲酯盐酸盐（贝尼地平盐酸盐，KW-3049）及一些钙拮抗剂从3H-尼群地平结合位点的解离速率。KW-3049从3H-尼群地平结合位点的解离比其他钙拮抗剂（即硝苯地平、尼群地平、尼伐地平、尼卡地平和尼索地平）更慢。平衡结合研究证实了KW-3049从3H-尼群地平结合位点的缓慢解离。当KW-3049与大鼠心脏膜预孵育时，其抑制效力增强了2.6倍，而硝苯地平并未改变其效力。在体内结合实验中，给大鼠施用KW-3049后，3H-尼群地平结合位点以剂量依赖性方式被占据，且在24小时后这种占据恢复到对照水平。这些受体结合研究结果与KW-3049的药理学特性一致。
