Elsevier

Biochemical Pharmacology

Volume 28, Issue 6, 15 March 1979, Pages 799-805
Biochemical Pharmacology

Interactions of chlorpromazine and imipramine with artificial membranes investigated by equilibrium dialysis, dual-wavelength photometry, and fluorimetry

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Abstract

Binding of chlorpromazine and imipramine to liposomes of various synthetic lipids was investigated by equilibrium dialysis, dual-wavelength photometry, and fluorimetry. As proved by equilibrium dialysis, liposomes of all investigated lipids bound chlorpromazine to a greater extent than imipramine. At temperatures above the lipid phase transition the membranes bound more of both drugs than they did below. These results were confirmed by dual-wavelength photometry at low drug concentrations. Chlorpromazine and imipramine fluidized lipid bilayers below their transition temperatures. Less imipramine bound to positively charged liposomes as compared with membranes of zwitterionic phosphocholine. This emphasizes the importance of ionic interactions for the binding of imipramine to lipid membranes. Chlorpromazine binding, however, was little affected by ionic interactions. Both chlorpromazine and imipramine had the same effect on the fluorescence of 1-anilino-8-naphthalene-sulfonate (a probe for the polar part of the membrane), whereas the fluorescence of perylene (a probe for the inner hydrocarbon region of bilayers) was quenched by chlorpromazine but not by imipramine. From the results obtained with the three complementary methods it is concluded that chlorpromazine binds to the surface of membranes and also penetrates into the inner hydrocarbon phase of the bilayer, whereas imipramine only binds near the surface of the liposomes.

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    Present address: Central Laboratory, Swiss Red Cross, Blood Transfusion Service, Wankdorfstrasse 10, CH-3000 Berne 22, Switzerland.

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