双嘧达莫在犬冠状动脉中的钙内流阻滞活性。

Calcium entry blocking activity of dilazep in dog coronary artery.

作者信息

Nakagawa Y, Gudenzi M, Mustafa S J

出版信息

Pharmacology. 1986;33(3):148-56. doi: 10.1159/000138212.

Abstract

Calcium entry blocking activities of adenosine and its potentiating compounds (dipyridamole, lidoflazine and dilazep) were studied in potassium (100 mmol/l) depolarized, dog, large coronary artery strips, in comparison to nifedipine, verapamil and diltiazem. Apparent pA2 values were calculated by using concentration-response curves for calcium before and 30 min after the addition of each dilator drug. The order of potency (using both pA2 and IC50 values) for the calcium entry blocking effect was: nifedipine greater than verapamil greater than diltiazem greater than lidoflazine greater than dilazep. Dipyridamole and adenosine had negligible calcium entry blocking activities (about 10,000 times less potent than verapamil). The calcium entry blocking activity of verapamil (using pA2 values) was 39.8 times less potent than nifedipine, and 3.6, 21.4 and 97.7 times more potent than diltiazem, lidoflazine and dilazep, respectively. The maximum relaxations induced by adenosine (3.7 X 10(-4) mol/l) and dipyridamole (5 X 10(-5) mol/l) were less than 20% that of 3 X 10(-4) mol/l papaverine. However, the other test drugs caused 80-90% relaxation under similar conditions. The relaxing effect of adenosine was inhibited by 8-phenyltheophylline (adenosine receptor antagonist) and potentiated by EHNA (an adenosine deaminase inhibitor), while dilazep-induced relaxation was not affected by these drugs. These findings suggest that the calcium entry blocking effect of dilazep in dog, large coronary artery strips is not mediated through adenosine.

摘要

在钾离子（100 mmol/l）去极化的犬大冠状动脉条上，研究了腺苷及其增效化合物（双嘧达莫、利多氟嗪和地拉卓）的钙通道阻滞活性，并与硝苯地平、维拉帕米和地尔硫䓬进行了比较。通过使用每种扩张剂药物添加前和添加后30分钟的钙浓度-反应曲线来计算表观pA2值。钙通道阻滞作用的效力顺序（使用pA2和IC50值）为：硝苯地平＞维拉帕米＞地尔硫䓬＞利多氟嗪＞地拉卓。双嘧达莫和腺苷的钙通道阻滞活性可忽略不计（效力约比维拉帕米低10000倍）。维拉帕米的钙通道阻滞活性（使用pA2值）比硝苯地平低39.8倍，分别比地尔硫䓬、利多氟嗪和地拉卓高3.6倍、21.4倍和97.7倍。腺苷（3.7×10⁻⁴ mol/l）和双嘧达莫（5×10⁻⁵ mol/l）诱导的最大舒张率小于3×10⁻⁴ mol/l罂粟碱诱导的最大舒张率的20%。然而，在类似条件下，其他受试药物可引起80 - 90%的舒张。腺苷的舒张作用被8-苯基茶碱（腺苷受体拮抗剂）抑制，并被EHNA（腺苷脱氨酶抑制剂）增强，而地拉卓诱导的舒张不受这些药物影响。这些发现表明，地拉卓在犬大冠状动脉条中的钙通道阻滞作用不是通过腺苷介导的。