Hypocholesterolemic action of a novel delta8-dihydroabietamide derivative, THD-341, in rats

The hypocholesterolemic properties of THD-341, N-(2,6-dimethylphenyl)-delta8-dihydroabietamide, were studied in rats. THD-341 reduced serum cholesterol levels in cholesterol-cholate-fed rats at a concentration of less than 0.001% in the diet or an oral dose of less than 3 mg/kg, once a day. When compared in terms of the 50% inhibitory dose for serum cholesterol elevation (ID 50%, % in diet), THD-341 (0.0008%) was comparable to D-thyroxine (0.0005%), more potent than estradiol (0.003%), and far more potent than clofibrate (0.2%), beta-sitosterol (0.8%), cholestyramine (2%), or nicotinic acid (3%). A daily intravenous injection of THD-341 was also effective (ID 50%: 7 mg/kg). THD-341 reduced serum and liver cholesterol in rats made hypercholesterolemic by 0.3% dietary thiouracil or 0.25% dietary cholate. Liver cholesteriol was more profoundly affected than the serum cholesterol. In normal rats, cholesterol was reduced in liver but not in serum. Its mechanism of action is unknown but the results suggest that THD-341 inhibits cholesterol absorption or re-absorption.