Possible Interaction: Chlorpromazine and Phosphatidic Acid

“ CPZ inhibited promotion of compensatory synthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), and also inhibited the synthesis of phosphatidic acid (PA).”

“This action might be partially a result of the inhibitory effect of CPZ on PA production.”

“With the [32P]labeled cells, however, PA-phosphohydrolase inhibitors, such as chlorpromazine and propranolol, could elicit large increases in labeled PA , indicating active PA metabolism in these cells.”

“ Chlorpromazine showed an apparent stimulation of accumulation of phosphatidic acid and CDP-diglycerides in microsomal membranes and phosphatidylglycerolphosphate in mitochondrial membranes in a concentration-dependent manner that was influenced by incubation time and the nature of fatty acids in CDP-diglycerides.”

“Evidence was obtained for the formation of a molecular complex between phosphatidic acid and chlorpromazine ; this was thought to be responsible for the protection from phosphatidate phosphohydrolase at the concentrations of chlorpromazine and Mg2+ examined.”

“From the kinetic analysis, the inhibition was found to be uncompetitive with respect to acyl-CoA. It was found that the … susceptible to the inhibitory action of chlorpromazine with unsaturated acyl-CoAs than with the saturated species, raising the possibility that chlorpromazine alters the … of phosphatidic acid produced … reaction.”

“The rate of incorporation of both [(32)P]orthophosphate and [2-(3)H)glycerol into phosphatidic acid and phosphatidylinositol increased by the administration of chlorpromazine.”

“These findings suggested that the administration of chlorpromazine increases the availability of phosphatidic acid by activating glycerophosphate acyltransferase and inhibiting phosphatidate phosphohydrolase, leading to enhanced synthesis of phosphatidylinositol.”