Effect of quinidine on membrane properties. Depression of the lipid phase transition temperature and changes in the permeability of the lipid bilayer.
The influence of an antiarrhythmic drug, quinidine, on the physical state of membrane phospholipids was investigated using model membranes, liposomes. Turbidimetric measurements on liposomes prepared from neutral (dipalmitoyl phosphatidylcholine) and acidic (dipalmitoyl phosphatidic acid) phospholipids showed that quinidine reduces the temp of the gel to liquid-crystalline phase transition and broadens the temp range of the transition. The effect of quinidine on the thermal behaviour of model membranes depends on both the pH and the type of phospholipids used. It is markedly stronger for acidic than for neutral phospholipids, suggesting the importance of electrostatic effects in drug-membrane interaction. The ability of quinidine to interact with the lipid bilayer was confirmed by permeability measurements with the use of a self-quenched fluorescent compound, calcein. It is suggested that quinidine-phospholipid interaction may contribute to the mechanisms by which the drug exerts its physiological and pharmacological effects.
D000818:Animals; D001921:Brain; D002417:Cattle; D005452:Fluoresceins; D007202:Indicators and Reagents; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes; D008968:Molecular Conformation; D010539:Permeability; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D011802:Quinidine; D013329:Structure-Activity Relationship; D013696:Temperature
D005452:Fluoresceins; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D011802:Quinidine; C007740:fluorexon