Response to the hypobetalipoproteinemic agent adamantyloxyphenyl piperidine in hyperlipemic rats

The hypobetalipoproteinemic activity of U-41,792 (1-[p-(1-adamantyloxy)-phenyl]-piperidine) is a marked and selective reduction of heparin precipitating lipoproteins (low density plus very low density lipoproteins) in cholesterol-cholic acid induced hypercholesterolemic rats. This activity consists of both a reduction in heparin precipitating lipoproteins (HPL) and an increase in high density lipoproteins that are not precipitated by heparin. The increase in high density lipoproteins is routinely noted by decreases in HPL/cholesterol ratios. The pattern of response following single 100 mg/kg doses of U-418792 was determined. After an I.V. dose was administered in a cottonseed oil emulsion, serum cholesterol levels were reduced, beginning at 8 hr after administration and persisting for 96 hr. Similar results, though delayed somewhat, were obtained after a single oral dose. Activity was accompanied by increases in weight and cholesterol content of livers. After multiple, daily, oral doses, liver weights, total lipids, and cholesterol contents were reduced. Hypobetalipopreteinmeic activity was enhanced by prolonged treatments as demonstrated by analyses of serum obtained weekly throughout 7 wk.