Molecular Pharmacology, Vol 20, 244-245, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Micellarization of Chlorpromazine

Implications in the Binding of the Drug to Brain Tubulin

¹ Department of Biophysics and Genetics, University of Colorado Medical Center, Denver, Colorado 80220, Department of Physical Biochemistry, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, and Department of Biochemistry, University of Queensland, St. Lucia, Queensland 4067, Australia

The micellar characteristics of chlorpromazine in 0.025 M sodium pyrophosphate-0.00125 M magnesium chloride-0.125 M sodium chloride-1.0 M sucrose, pH 6.8, 37°, have been investigated by frontal gel chromatography on Sephadex G-25. Results indicate a critical micelle concentration of 0.2 mM, a value that substantiates the necessity to consider the coexistence of monomeric and micellar forms of the drug in its interaction with tubulin under these conditions. Taken in conjunction with published results of such binding studies, this investigation provides experimental support for the concept that the micellar state of chlorpromazine interacts preferentially with one site on brain tubulin.