Comparison of perturbation effect of propranolol, verapamil, chlorpromazine and carbisocaine on lecithin liposomes and brain total lipid liposomes. An EPR spectroscopy study.
Effect of verapamil, propranolol, chlorpromazine and carbisocaine on dynamics and/or order of liposomes (perturbation effect), prepared from different molar ratios of lecithin (PC) and rat brain total lipids (TL) was studied by EPR spectroscopy using spin probes 16-doxyl stearic acid and 14-doxyl phosphatidylcholine. The PC liposomes had higher dynamics and/or lower order than the TL liposomes. The perturbation effect of the drugs depended largely on the lipid composition of the liposomes. The drugs at the drug/lipid molar ratios from 0.1 to 1 increased membrane dynamics and/or decreased membrane order. The drugs had the most pronounced perturbation effect in the liposomes prepared from brain total lipids. The effect of the drugs decreased with decreasing the TL/PC ratio in the liposomes and was lowest, almost diminished, in the PC liposomes. Increasing concentration of the drugs decreased the difference between the dynamics and/or order of the PC and TL liposomes and so eliminated the influence of lipid composition on these membrane parameters. The results emphasize the role of lipid composition in studies concerning drug-lipid interactions in model and biological membranes.
Ondrias
K
K
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Stasko
A
A
Misík
V
V
Reguli
J
J
Svajdlenka
E
E
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D008081:Liposomes / Q000378:metabolism*; D008970:Molecular Weight; D010713:Phosphatidylcholines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology*
D002219:Carbamates; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; C046030:carbizocaine; D011433:Propranolol; D014700:Verapamil; D002746:Chlorpromazine