Hypocholesteremic effect of phenoxybenzamine (dibenzyline), an adrenergic blocking agent. Experimental studies with monkeys and human volunteers.

Abstract

The effect of an orally effective adrenergic blocking agent, Dibenzyline, on serum cholesterol levels was studied in human subjects and in monkeys on high-fat diets. In addition, the effect of the phenoxyethyl analogue of Dibenzyline, G-D 131, was also investigated in monkeys. The studies showed that the increase in serum cholesterol level brought about by a high-fat diet in monkeys could be considerably reduced by supplementation with Dibenzyline. This hypocholesteremic action was also observed with the analogue of Dibenzyline, G-D 131, which does not possess the adrenergic blocking property. It appears, therefore, that the hypocholesteremic action of Dibenzyline is independent of its adrenergic blocking activity. When a high-fat diet which also contained a high amount of cholesterol was used, Dibenzyline retarded the increase in serum cholesterol of monkeys for a considerable length of time. Administration of Dibenzyline, 10 mg. daily for 11 days, brought about a fall in serum cholesterol in two of the three human subjects and arrested the further increase in serum cholesterol in the third subject on a high-butterfat diet. All the subjects showed increased fecal elimination of cholic and dihydroxycholanic acids during the Dibenzyline-supplemented period, suggesting that the hypocholesteremic effect of the drug is at least partly mediated through increased elimination of cholesterol as bile acids.