Effect of AY 9944 and chlorpromazine on Concanavalin A-induced stimulation of human lymphocytes.

Amphiphilic molecules AY 9944 and chlorpromazine (CPZ) inhibited DNA synthesis in Concanavalin A-stimulated lymphocytes in a dose-dependent manner. While AY 9944 strongly decreased 7-dehydrocholesterol conversion to cholesterol, CPZ did not significantly affect this reaction. Moreover, the inhibitory effect of AY 9944 and CPZ on DNA synthesis took place in the presence of cholesterol in the culture medium. These findings suggest that the mechanism of inhibition of DNA synthesis by AY 9944 or CPZ is not related to endogenous cholesterol synthesis or exogenous cholesterol supply. Results are discussed in relation to the amphiphilic properties of AY 9944 and CPZ and to the interaction of these drugs with membranes or other intracellular targets such as calmodulin.