The hypolipidemic activity of 3-iminophthalimidine in rodents.

3-Immophthalimidine (3-imino-2,3-dihydroisoindol-l-one) was examined for its hypolipidemic activity in rodents as a chemical modification of the phthalimide nucleus. Administration of 3-iminophthalimidine for 16 days, at 20 mg/kg/day, demonstrated potent hypolipidemic activity, decreasing serum cholesterol and triglyceride levels by 44 % and 41 %, respectively. No effects on organ or body weight, or food consumption were noted as a result of administration of this agent to rats. However, reductions of liver lipid levels, i. e., triglycerides and neutral lipids, as well as lipid content of serum lipoprotein fractions, i. e., cholesterol, triglyceride and neutral lipids, were observed following administration of this agent. An increase was noted in fecal excretion of cholesterol and/or its metabolites. This effect was not correlated with an increase in bile acid synthesis, but may due in part to increased biliary excretion of cholesterol. Significant inhibitory effects of 3-iminophthalimidine on liver enzyme activities were noted, including acetyl CoA carboxylase and sn-glycerol-3-phosphate acyl transferase. Mitochondrial citrate exchange was also greatly reduced at low concentrations of the agent. Inhibition at these sites could account for the reduction in serum triglyceride levels observed after treatment in rodents.