Molecular Pharmacology, Vol 11, 256-267, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Interaction of Chlorpromazine with Brain Microtubule Subunit Protein

¹ Department of Biophysics and Genetics, University of Colorado Medical Center, Denver, Colorado 80220

Chlorpromazine at concentrations which approximate apparent physiological concentrations interacts reversibly with brain microtubule subunit protein in vitro and, in so doing, inhibits the rate of reassembly of microtubules and the binding of colchicine by the protein. It also causes dissassembly of microtubules formed in the absence of the drug. These results appear to provide a molecular explanation for inhibition by chlorpromazine of fast axonal transport of proteins in vitro in frog sciatic nerve, and provide a fresh clue as to the primary mechanism for the psychotropic effect of this drug.