Spedding M
Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):464-6. doi: 10.1007/BF00692917.
The kinetics of the interactions between Bay K 8644, a calcium channel activator, and the "calcium-antagonists" nifedipine, verapamil and diltiazem have been investigated. Nifedipine shifted cumulative concentration-response curves for Ca2+ to the right in K+ depolarized taenia preparations from the guinea-pig caecum. The apparent pA2 was 9.3 +/- 0.2 (slope 1.44; 95% confidence limits 0.99-1.88). Bay K 8644 (10-1,000 nmol/l) reduced the inhibitory effects of nifedipine, shifting the Schild plots to the right, without affecting the slope of the nifedipine:Ca2+ interaction. Thus, the interaction between the dihydropyridines was independent of external Ca2+. The parallel shifts of the Schild plots allow a novel interpretation of the "agonist" potency of Bay K 8644 because the compound had an apparent pA2 of 8.8 (slope 0.92) as an "antagonist" of the inhibitory effects of nifedipine. In contrast, Bay K 8644 was a non-competitive antagonist of the inhibitory effects of verapamil and diltiazem on Ca2+-induced contractions. These findings emphasize the differences between the various classes of "calcium-antagonists" and show that Bay K 8644 is a powerful tool discriminating between them.
对钙通道激活剂Bay K 8644与“钙拮抗剂”硝苯地平、维拉帕米和地尔硫䓬之间相互作用的动力学进行了研究。在豚鼠盲肠的K⁺去极化绦虫制剂中，硝苯地平使Ca²⁺的累积浓度 - 反应曲线右移。表观pA₂为9.3±0.2（斜率1.44；95%置信限0.99 - 1.88）。Bay K 8644（10 - 1000 nmol/L）减弱了硝苯地平的抑制作用，使Schild图右移，但不影响硝苯地平与Ca²⁺相互作用的斜率。因此，二氢吡啶类之间的相互作用与细胞外Ca²⁺无关。Schild图的平行移动使得对Bay K 8644的“激动剂”效力有了新的解释，因为该化合物作为硝苯地平抑制作用的“拮抗剂”时，表观pA₂为8.8（斜率0.92）。相比之下，Bay K 8644是维拉帕米和地尔硫䓬对Ca²⁺诱导收缩抑制作用的非竞争性拮抗剂。这些发现强调了各类“钙拮抗剂”之间的差异，并表明Bay K 8644是区分它们的有力工具。
