Kojda G, Klaus W, Werner G, Fricke U
Institut für Pharmakologie, Universität zu Köln, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Oct;344(4):488-94. doi: 10.1007/BF00172590.
It has been reported that the lipophilicity of dihydropyridine-type calcium entry blockers may influence both their negative inotropic and their vasodilator activities. The action of nitrendipine and six related 3-ester side-chain derivatives with increasing alkyl and aryl substituents have been investigated in isolated porcine trabecular muscles and coronary artery rings. The lipophilicity of the drugs was determined by high-pressure liquid chromatography. In addition, some sterical parameters of the ester derivatives were considered. For the drugs tested, an increase in 3-ester side chain volume correlated well with increasing lipophilicity. Compared to nitrendipine, vascular selectivity of the ester side-chain derivatives, as expressed by the ratio of their negative inotropic and vasodilator activities, was much reduced. Neither vasodilator nor negative inotropic activity was directly related to the corresponding lipophilicity. Based on these results, earlier suggestions about the influence of the ester side-chain in dihydropyridines on their cardiovascular profile are extended.
据报道，二氢吡啶类钙通道阻滞剂的亲脂性可能会影响其负性肌力作用和血管舒张活性。已在离体猪小梁肌和冠状动脉环中研究了尼群地平和六种具有增加烷基和芳基取代基的相关3-酯侧链衍生物的作用。通过高压液相色谱法测定药物的亲脂性。此外，还考虑了酯衍生物的一些空间参数。对于所测试的药物，3-酯侧链体积的增加与亲脂性的增加密切相关。与尼群地平相比，酯侧链衍生物的血管选择性（以其负性肌力作用与血管舒张活性的比值表示）大大降低。血管舒张活性和负性肌力作用均与相应的亲脂性无直接关系。基于这些结果，关于二氢吡啶类中酯侧链对其心血管特性影响的早期观点得到了扩展。
