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A single oral dose of a new hypolipidemic agent, 4-(cis-p-menthan-8)benzanilide (YM-95831) exhibited a marked elevation of high density lipoprotein (HDL) cholesterol with great reduction of serum total cholesterol in rats which were fed hypercholesterolemic diet. Reduction of serum total cholesterol preceded the increase in HDL, reached a peak at 16 h and was still significant even after 112 h. When YM-95831 was orally given daily for 4 days to the hypercholesterolemic rats, the dose required to reduce serum total cholesterol by 50% was about 6 mg/kg. Clofibrate was more than 10 times less potent than YM-95831 in the hypolipidemic activity. Nicotinic acid was virtually ineffective. HDL cholesterol was doubled by YM-95831 of about 3 mg/kg, but not significantly influenced by clofibrate of 200 mg/kg. Nicotinic acid at 400 mg/kg increased 1.5 times HDL cholesterol. Polyacrylamide gel electrophoresis of the serum demonstrated the decrease in beta-lipoprotein and the increase in alpha-lipoproteins by YM-95831. In hypercholesterolemic rats. YM-95831 increased preferentially HDL2 (d: 1.063-1.125) without significant alteration of a HDL3 (d: 1.125-1.21) level. YM-95831 tempted to decrease liver total cholesterol. Nicotinic acid significantly decreased the cholesterol whereas clofibrate exhibited no alteration. These results indicate that YM-95831 is a potent and long-lasting hypolipidemic agent with a potent HDL cholesterol elevating activity.


I Ohata, N Sakamoto, R Nitatori, H Maeno. Aminophenyl ether compound (YM-95831), a new hypolipidemic agent with a high density lipoprotein elevating activity in rats. Arzneimittel-Forschung. 1983;33(2):237-41

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PMID: 6682662

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