Changes in liver lipids after administration of 2-decanoylamino-3-morpholinopropiophenone and chlorpromazine

The enzyme which forms glucocerebroside, ceramide: UDP-glucose glucosyltransferase, is inactivated in vitro by a cationic analog of cerebroside, 2-decanoylamino-3-morpholinopropiophenone. A study of the inhibitor using intraperitoneal injection into young mice showed that the level of the enzyme activity in liver was appreciably lowered between 3 and 6 hr after injection. The activity increased subsequently, overshooting the normal level within 24 hr by about 20%, then returning to normal within the next 24 hr. Additional effects observed in liver were an increase in lipid content (primarily in the triglyceride fraction and ceramides) and a decrease in the glucocerebroside level. Body temperature dropped rapidly. Markedly similar effects were produced by injecting chlorpromazine, which was tried in order to reduce the hyperirritability and inhibitory effects on monoamine oxidase previously demonstrated by the glucosyltransferase inhibitor. Chlorpromazine did indeed block the hyperirritability and resulted in enhancement of the keto amine's effects on the enzyme and lipids. It is possible that the two drugs in combination would be helpful in ameliorating the symptoms due to the cerebroside accumulation that occurs in Gaucher disease. Diazepam also produced a reduced level of glucosyltransferase. A color reaction for chlorpromazine, possibly suitable for quantitative determination in tissues, was accidentally discovered.