Dzimiri N
Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Res Commun Chem Pathol Pharmacol. 1993 Apr;80(1):121-4.
The effects of three class I antiarrhythmic drugs procainamide, tocainide and phenytoin on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. Tocainide inhibited the ATPase activity in the range of 1.0 nM-500 mM, exhibiting IC20 and IC50 values of 9.4 +/- 0.7 microM and 5.2 +/- 0.4 mM, while procainamide exhibited significant (p < 0.05) inhibitory effect only at concentrations above 1.0 mM with IC20 and IC50 values of 35.4 +/- 2.7 mM and 90.8 +/- 3.7 mM, respectively. On the other hand, phenytoin inhibited the enzyme by 17% and 8% at 1.0 nM and 1.0 microM respectively, while it stimulated it at higher concentrations, thereby increasing its activity by 10%, 57% and 227% at 10, 100, 1000 microM, respectively. The inhibitory actions of these drugs are probably related to their lipophilicity and membrane stabilizing activity, while the stimulatory effect of phenytoin suggests some specific interaction with some component(s) of the oxidative phosphorylation or respiratory chain.
在豚鼠心脏制剂中评估了三种I类抗心律失常药物普鲁卡因胺、妥卡尼和苯妥英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。妥卡尼在1.0 nM至500 mM范围内抑制ATP酶活性，IC20和IC50值分别为9.4±0.7 microM和5.2±0.4 mM，而普鲁卡因胺仅在浓度高于1.0 mM时表现出显著（p<0.05）抑制作用，IC20和IC50值分别为35.4±2.7 mM和90.8±3.7 mM。另一方面，苯妥英在1.0 nM和1.0 microM时分别抑制该酶17%和8%，而在较高浓度下刺激该酶，从而在10、100、1000 microM时分别使其活性增加10%、57%和227%。这些药物的抑制作用可能与其亲脂性和膜稳定活性有关，而苯妥英的刺激作用表明其与氧化磷酸化或呼吸链的某些成分存在一些特异性相互作用。
