Depression of Phase-transition Temperature in a Model Cell Membrane by Local Anesthetics

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Abstract
The fluidizing effects of local anesthetics on dipalmitoyl lecithin (DPL) bilayer dispersion was studied by measuring the turbidity change. Tetracaine, bupivacaine, lidocaine and procaine were studied. They all depressed the phase-transition temperature. The binding of the drugs to the model membrane followed unsaturable kinetics, and the pH titration curve showed that only uncharged molecules were active. The freezing point depression was analyzed according to the Van''t Hoff model. From this model, the partition coefficients of the uncharged molecules between DPL and water were estimated: lidocaine 76, procaine 159, bupivacaine 812 and tetracaine 1405. The concentration of local anesthetics in the DPL phase needed to decrease the phase-transition temperature 1.degree. C showed a constant value of 0.132 M. The concentration of local anesthetics in the DPL phase was a function of pH, partition coefficient and volume ratio between the DPL and aqueous phases. The normalized values of the fluidizing action of these drugs at physiologic conditions correlated well with their nerve-blocking potencies. The uncharged molecules fluidized the lecithin membrane by unsaturable nonspecific binding. The possible effect of the charged molecules upon the fluidity of natural membranes was not established.

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