Ishii A, Toyama J
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Nagoya, Japan.
J Cardiovasc Pharmacol. 1993 Feb;21(2):191-6.
Benidipine is a newly developed slow-onset and long-lasting dihydropyridine calcium antagonist. The kinetics of specific binding of (+/-)[3H]benidipine to the dihydropyridine receptor sites in rat heart membranes were assessed. The dissociation constant (Kd) and the maximal number of binding sites were 0.078 +/- 0.029 nM and 286 +/- 6 fmol/mg of protein, respectively. Association and dissociation rate constants of (+/-)[3H]benidipine binding were 4 and 50 times smaller, respectively, than those of (+/-)[3H]nitrendipine binding. In displacement studies, the decreasing order of potency was benidipine, nisoldipine, nicardipine, nitrendipine, nifedipine, and Bay K 8644. A high stereoselectivity was observed, with Ki values of 0.028 nM in the S-S-(+) isomer and 4.4 nM in the R-R-(-) isomer of this drug. Benidipine had a high affinity for specific binding, with an inhibition constant of 0.084 nM, which was in good agreement with the Kd value stated above. Among the stimulants and blockers of alpha- and beta-adrenergic, cholinergic, histaminergic, dopaminergic, serotonergic, or GABAergic receptors, no drug inhibited or enhanced specific (+/-)[3H]benidipine binding. These binding properties of (+/-)[3H]benidipine may explain its unique slow onset and long-lasting antihypertensive activities.
贝尼地平是一种新开发的起效缓慢且作用持久的二氢吡啶类钙拮抗剂。评估了（±）[³H]贝尼地平与大鼠心脏膜中二氢吡啶受体位点特异性结合的动力学。解离常数（Kd）和最大结合位点数分别为0.078±0.029 nM和286±6 fmol/mg蛋白质。（±）[³H]贝尼地平结合的缔合速率常数和解离速率常数分别比（±）[³H]尼群地平结合的速率常数小4倍和50倍。在置换研究中，效力递减顺序为贝尼地平、尼索地平、尼卡地平、尼群地平、硝苯地平以及Bay K 8644。观察到了高立体选择性，该药物的S-S-（+）异构体的Ki值为0.028 nM，R-R-（-）异构体的Ki值为4.4 nM。贝尼地平对特异性结合具有高亲和力，抑制常数为0.084 nM，这与上述Kd值高度一致。在α和β肾上腺素能、胆碱能、组胺能、多巴胺能、5-羟色胺能或γ-氨基丁酸能受体的激动剂和阻滞剂中，没有药物抑制或增强特异性（±）[³H]贝尼地平结合。（±）[³H]贝尼地平的这些结合特性可能解释了其独特的起效缓慢和持久的降压活性。
