Formation of micelles and membrane action of the local anesthetic tetracaine hydrochloride.

The formation of micelles of the local anesthetic tetracaine hydrochloride in aqueous phosphate buffer solution of pH 6.5 and ionic strength (I) 0.10 was examined at 22 degrees C by surface tension and using the fluorescent indicators perylene (peri-dinaphthalene) and 8-anilino-1-naphthalene sulfonic acid, sodium salt (ANS). The critical micelle concentration was located at 0.069, 0.071 and 0.063 M by measurements of surface tension, perylene solubilization and enhancement of ANS fluorescence, respectively. In contrast to other cationic surfactants, the anesthetic monomer did not show evidence of forming a fluorescent molecular complex with ANS under the experimental conditions of this study. The formation of micelles by tetracaine-HCl showed a pronounced effect on lipid membranes by inducing an abrupt decrease in the scattered light of egg lecithin liposomes at an anesthetic concentration roughly similar to its critical micelle concentration. This optical behaviour is characteristic of liposome damage and can be interpreted to mean that the lipids become solubilized into tetracaine-HCl micelles. The ability of this local anesthetic to form micelles can be taken as a manifestation of the same hydrophobic forces that lead to partitioning of the drug into membranes.