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ISSN electronic edition: 1336-9075
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Influence of chlorpromazine and its derivatives on the dynamics of lipid-membranes

K. Ondriaš, J. Reguli, A. Staško, E. Švajdlenka, J. Pogády, and D. Martišová

a Institute of Experimental Pharmacology, Centre of Physiological Sciences Slovak Academy of Sciences, CS-842 16 Bratislava

 

Abstract: Perturbation effect of the tranquilizers chlorpromazine, chlorprothixene, levopromazine, thioridazine, and perfenazine on lipid membranes was studied using the electron spin resonance spectroscopy of stearic acid spin labeled at the position 16. The order parameter S of the spin probe in the lipid membranes depending either on the membrane order and/or dynamics of the hydrophobic membrane part was used to estimate the perturbation effect of the drugs. Chlorpromazine increased the order parameter S of the probe in lecithin liposomes, and decreased the parameter S in the liposomes prepared from the rat brain total lipid/lecithin mixtures. The disordering effect of chlorpromazine increased with the increase of the total lipid/lecithin mass ratio in the liposomes. The tranquilizers showed different propensities to decrease the S parameter of the probe in the liposomes prepared from the total lipids. The propensities with the individual compounds increase in the order: perfenazine, levopromazine ~ chlorprothixene ~ chlorpromazine, thioridazine. The different propensities of the drugs may be explained by their structure, depending on the hydrogen bonds spanned between the headgroups of lipids and by their incorporation into the membranes.

Full paper in Portable Document Format: 432a315.pdf

 

Chemical Papers 43 (2) 315–324 (1989)

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