Molecular Pharmacology, Vol 13, 474-487, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Local Anesthesia: The Interaction between Phospholipids and Chlorpromazine, Propranolol, and Practolol

¹ Department of Physiology and Biochemistry, University of Southampton, Southampton SO9 3TU, England

Chlorpromazine and propranolol have been shown to reduce the temperature of the gel to liquid-crystalline phase transition in dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylethanolamine, at concentrations comparable to those that block sodium conductance in nerve. Effects on the transition temperatures with increasing concentration are nonlinear because of the buildup of positive charge on the liposomes. Addition of myristic acid to the liposomes reduces this charge effect and so increases the binding of chlorpromazine and propranolol; the effect of myristic acid is masked by addition of Ca²⁺. In contrast, pnactolol at concentrations up to 20 mM has no effect on lipid phase transition temperatures, and has little local anesthetic activity. These anesthetic effects are discussed in terms of the annular transition model; the sodium channel is postulated to be surrounded by an annulus of lipid in the gel state, the rigid lipid microenvironment ensuring maintenance of the optimum configuration for the channel. Addition of anesthetics triggers a change in the lipid annulus from the gel to the liquid-crystalline state, with concomitant relaxation of the protein and reduction in the size of the channel.

Note:
ACKNOWLEDGMENTS I thank ICI Pharmaceuticals Division for the samples of propranolol and practolol.

This article has been cited by other articles:

				T. Heimburg and A. D. Jackson The Thermodynamics of General Anesthesia Biophys. J., May 1, 2007; 92(9): 3159 - 3165. [Abstract] [Full Text] [PDF]