Hypolipidemic activity of 3- and 4-phenyl-piperidine-2,6-diones and selected N-substituted derivatives.

Three- and 4-phenyl-piperidine-2,6-dione derivatives were investigated for hypolipidemic activity at 20 mg/kg/day intraperitoneally in rodents. The 3-phenyl compound afforded the best activity and effectiveness in both normal and hyperlipidemia-induced mice. The agent lowered lipids by blocking the de novo hepatic synthesis of cholesterol and triglycerides, specifically at the sites of ATP-dependent citrate lyase, acetyl CoA synthetase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. The agent caused a more rapid clearance of cholesterol by the fecal route. Cholesterol levels of the chylomicrons, very low density lipoprotein and low density lipoprotein (LDL) were reduced, whereas high density lipoprotein cholesterol was significantly elevated after drug administration. Triglyceride content was lowered in the chylomicron and LDL fractions. These modulations of lipid content of serum lipoproteins by the drug suggest a favorable situation for treatment of hyperlipidemic states.