I类抗心律失常药物对豚鼠心脏标本中线粒体ATP酶活性的影响。

Effects of class I antiarrhythmic drugs on mitochondrial ATPase activity in guinea pig heart preparations.

Almotrefi A A

Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.

Gen Pharmacol. 1993 Jan;24(1):233-7. doi: 10.1016/0306-3623(93)90040-5.

Abstract

The effects of three class I antiarrhythmic drugs quinidine, lidocaine and lorcainide on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase, EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. 2. All three drugs inhibited the enzyme activity in a concentration-dependent fashion. 3. Lorcainide was the most potent, exerting inhibitory effects in the range of less than 1.0 nM-2.0 mM, with IC20 and IC50 values of 9.4 +/- 0.6 nM and 87.2 +/- 5.5 microM. However, in the range of approx. 10 nM-10 microM, the enzyme response decreased only slightly with increasing lorcainide concentrations. 4. Quinidine and lidocaine, on the other hand, inhibited the enzyme activity in the range of 1.0 microM-100 mM. 5. The IC20 and IC50 values for quinidine were 0.92 +/- 0.04 mM and 4.8 +/- 0.6 mM and for lidocaine were 115 +/- 6 microM and 2.3 +/- 0.3 mM. 6. The results show that all three drugs inhibit mitochondrial ATPase activity and that lorcainide is the most potent. 7. These inhibitory effects may be related to the lipophilicity and membrane stabilizing activity of this class of antiarrhythmic drugs.

摘要

在豚鼠心脏制剂中评估了三种I类抗心律失常药物奎尼丁、利多卡因和劳卡尼对未受损心肌线粒体ATP酶[ATP：磷酸水解酶，EC 3.6.1.3]活性的影响。2. 这三种药物均以浓度依赖性方式抑制该酶活性。3. 劳卡尼的作用最强，在小于1.0 nM至2.0 mM的范围内发挥抑制作用，其IC20和IC50值分别为9.4±0.6 nM和87.2±5.5 μM。然而，在约10 nM至10 μM的范围内，随着劳卡尼浓度的增加，酶反应仅略有下降。4. 另一方面，奎尼丁和利多卡因在1.0 μM至100 mM的范围内抑制该酶活性。5. 奎尼丁的IC20和IC50值分别为0.92±0.04 mM和4.8±0.6 mM，利多卡因的IC20和IC50值分别为115±6 μM和2.3±0.3 mM。6. 结果表明，这三种药物均抑制线粒体ATP酶活性，且劳卡尼的作用最强。7. 这些抑制作用可能与这类抗心律失常药物的亲脂性和膜稳定活性有关。