Amiodarone induced modifications of the phospholipid physical state. A fluorescence polarization study

The effects of an antiarrhythmic and antianginal drug, amiodarone, on the physical state of membrane phospholipids was investigated by means of fluorescence polarization using the apolar probe 1,6 diphenyl-1,3,5-hexatriene incorporated in the hydrocarbon core. Multilamellar vesicles were prepared from neutral phospholipids (egg phosphatidylcholine, synthetic saturated phosphatidylcholine) alone or mixed with cholesterol or various lipids representative of the main lipid classes. Amiodarone reduces the temperature of the gel to liquid-crystalline phase transition and either increases or decreases lipid mobility in the gel or liquid-crystalline phase. In the gel state, the lipid mobility depends on drug concentration, degree of ionization and the length of the lipid acyl chains. In the liquid-crystalline state, the decreased lipid mobility which is concentration-dependent is essentially due to hydrophobic interactions. Amiodarone increases the lipid order parameter to the same extent as cholesterol. The data suggested that amiodarone is a rigid molecule deeply buried in the hydrocarbon core of the lipid and that amiodarone-lipid interactions are mainly hydrophobic.