BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-
acetamide], a new
hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and
hyperlipidemia in rats, and in the
cholesterol-induced
atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced
hyperlipidemia, 50 mg
BR-931 per kg was equieffective as 200 mg of
clofibrate (CPIB) per kg. In contrast with CPIB,
BR-931 exerted a powerful antilipolytic activity against
epinephrine,
ACTH,
nicotine and cold exposure.
BR-931 was particularly effective in diet-induced
hyperlipidemias.
Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced
hypercholesterolemia and
hypertriglyceridemia. In these last two tests, the distribution of
lipoprotein cholesterol was also determined. CPIB did not affect
HDL cholesterol levels that had been decreased by the diets; in contrast,
BR-931, already at doses of 50 mg/kg, brought the HDL/total
cholesterol ratio back toward normal. A significant
HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in
cholesterol-fed rabbits.
BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine
acetyltransferase, appears to be a
hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of
hyperlipidemias and
atherosclerosis.