X-ray studies on phospholipid bilayers. XIV. Interactions with the antiarrhythmic asocainol.

Asocainol (ASOC) belongs to class I of the antiarrhythmic drugs, i.e., those that exert their action at the level of the sodium channels of the myocardial cell membrane. It has been suggested that their molecular mechanism of action might be through nonspecific interactions with phospholipids that surround the channel proteins. In order to test this hypothesis, ASOC was made to interact with two multibilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE). These are the type of lipids that are respectively found in the outer and inner monolayers of human erythrocytes. The experiments were carried out in a hydrophobic as well as in a hydrophilic medium below the phospholipid main transition temperatures. The perturbing effect of ASOC upon the bilayer structures was determined by X-ray diffraction. It was found that ASOC was able to fluidize DMPC in both media but not to DMPE.