Hypolipidemic activity of 6-substituted 6,7-dihydro-5H-dibenz[c,e]azepine and the effects of 6,7-dihydro-5H-dibenz[c,e]azepine on lipid metabolism of rodents.

A series of 6-substituted derivatives of 6,7-dihydro-5H-dibenz[c,e]azepine was found to be active hypolipidemic agents in rodents at doses of mg/kg per day. The parent drug was found to suppress the enzyme activity of ATP-dependent citrate lyase, sn-glycerol-3-phosphate acyl transferase, and phosphatidate phosphohydrolase. Treatment with 6,7-dihydro-5H-dibenz[c,e]azepine resulted in a reduction of cholesterol, neutral lipid, and triglyceride content in mouse and rat liver. The agent also afforded a reduction in cholesterol, triglycerides and neutral lipids in the chylomicron and very low density lipoprotein (VLDL) fractions. In the high density lipoprotein (HDL) fraction, the triglyceride, neutral lipids, and phospholipids were lowered but the cholesterol content was not. [H3]Cholesterol distribution studies showed that the 3H-content was lowered in the major organs but was elevated in the chyme and stomach, suggesting that the drug accelerated bile secretion of cholesterol or its metabolites.