Effect of chlorpromazine on rat arterial lipid synthesis,in vitro

The effect of chlorpromazine, a major tranquilizer, on arterial lipid metabolism was studied in vitro in rat aortas incubated with ¹⁴C] acetate and ¹⁴C] mevalonate as lipid precursors. Chlorpromazine at a level of 0.25 mM in the incubation medium significantly reduced the incorporation of ¹⁴C] acetate into free fatty acids (p<0.01) and total phospholipids (p<0.001) but not triglycerides. Chlorpromazine also altered the pattern of arterial phospholipids synthesized from ¹⁴C] acetate by significantly increasing the relative proportion of phosphatidylinositol plus phosphatidylserine (p<0.02) and reducing the relative proportion of sphingomyelin (p<0.001). ¹⁴C] Acetate incorporation into the combined fractions of steryl esters plus hydrocarbons and sterols plus diglycerides was also significantly reduced (p<0.001) by 0.25 mM chlorpromazine. Studies with ¹⁴C] mevalonate showed that chlorpromazine is also an inhibitor of sterol biosynthesis in arterial tissues as evidenced by 35–40% reductions (p<0.05) in the formation of¹⁴C-labeled squalene and C₂₇ sterols.