Suwalsky M, Sánchez I, Bagnara M, Sotomayor C P
Faculty of Chemical Sciences, University of Concepción, Chile.
Biochim Biophys Acta. 1994 Nov 2;1195(2):189-96. doi: 10.1016/0005-2736(94)90255-0.
Several hypotheses link the molecular mechanism of action of the antiarrhythmic drugs (AAD) that belong to class I to nonspecific interactions with phospholipids sited in the neighborhood of the sodium channels in the membrane of the myocard. The interactions of asocainol (ASOC), procainamide (PROC) and quinidine (QUIN) with: (a) multibilayers of dimyristoylphosphatidylcholine (DMPC) and of dimyristoylphosphatidylethanolamine (DMPE), in both a hydrophobic and a hydrophilic medium, and (b) DMPC vesicles, were studied, respectively, by X-ray diffraction and fluorescence spectroscopy. It was found that the three AAD interacted with the lipid bilayers. However, the extension of these interactions depended on the nature and concentration of the lipids and AAD as well as on the medium where the interactions were performed. The different capacity of ASOC and PROC to perturb the bilayer structures, mainly that of DMPC, indicated that the interactions were strongly dependent on the lipophilicity of these drugs. The fact that QUIN did not completely interact in accordance to its lipophilicity suggested that other factors also play a role in these interactions. It is concluded that it may be valid the suggested molecular mechanisms of action of class I AAD involving their interaction with the membrane phospholipids.
有几种假说将属于I类的抗心律失常药物（AAD）的分子作用机制与心肌细胞膜中钠通道附近的磷脂的非特异性相互作用联系起来。分别通过X射线衍射和荧光光谱法研究了阿索卡诺（ASOC）、普鲁卡因胺（PROC）和奎尼丁（QUIN）与：（a）在疏水和亲水介质中的二肉豆蔻酰磷脂酰胆碱（DMPC）和二肉豆蔻酰磷脂酰乙醇胺（DMPE）多层膜，以及（b）DMPC囊泡的相互作用。发现这三种AAD与脂质双层相互作用。然而，这些相互作用的程度取决于脂质和AAD的性质和浓度以及进行相互作用的介质。ASOC和PROC扰乱双层结构（主要是DMPC双层结构）的能力不同，这表明这些相互作用强烈依赖于这些药物的亲脂性。奎尼丁没有完全按照其亲脂性进行相互作用，这一事实表明其他因素在这些相互作用中也起作用。得出的结论是，所提出的I类AAD涉及它们与膜磷脂相互作用的分子作用机制可能是有效的。
