Molecular Pharmacology, Vol 19, 295-301, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

A Comparative Study of the Interaction of Chlorpromazine, Trifluoperazine, and Promethazine with Mouse Brain Tubulin

¹ Department of Biophysics and Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80262

The comparative interaction of chlorpromazine, trifluoperazine, and promethazine with mouse brain tubulin has been examined via their effects on the assembly of tubulin in vitro, the circular dichroism of tubulin under nonpolymerizing conditions, and the fluorescence intensity of the protein. Of the two tranquilizing drugs, the more potent trifluoperazine inhibits assembly more strongly than does chlorpromazine, whereas the nontranquilizing drug promethazine does not inhibit but instead enhances assembly somewhat. Likewise, trifluoperazine has a stronger effect on the far-ultraviolet circular dichroic spectrum than does chlorpromazine, whereas promethazine is without effect. Thus, there are two separate correlations between biophysical measurements and the clinical potencies of these three phenothiazines. The fluorometric measurements, in turn, correlate in a provocative way with the assembly and circular dichroism results. The possible biological significance of these findings is discussed.

Note:
ACKNOWLEDGMENTS The authors thank Mr. Robert O. Coombs for technical assistance, Dr. Jerry L. Brown for use of his spectrofluorometer for early measurements, and Dr. Philip G. Archer for mathematical consultation.