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- W2275455478 abstract "A new hypolipidemic agent, 4-(cis-p-menthan-8-yloxy)benzanilide (YM-95831) and solid dispersed YM-95831 (sd-YM-95831, YM-95831/Excipient ratios=l:4) which was improved for its intestinal absorption were evaluated for their hypolipidemic activity in several hyperlipidemic animal models. The mode of the action was postulated.1)The hypolipidemic effect of sd-YM-95831 was about 2 times more potent than YM-95831 (raw material) in hypercholesterolemic rats.2)When sd-YM-95831 was given orally to normal rats for 5 weeks, the serum total cholesterol (TC) was decreased by 31% with a decrease in the atherogenic index (AI) by about 44% at a dose of 100 mg/kg. sd-YM-95831 decreased liver TC and triglycerides (TG) in dose-dependent manner up to 100 mg/kg in normal rats.3)In the glycerol-induced hyperlipidemic rats, sd-YM-95831 decreased serum TC with a decrease in the Al. In the triton-induced hyperlipidemic rats, sd-YM-95831 was about 2 times more potent than clofibrate in the hypolipidemic activity.4)sd-YM-95831 in a dose of 50mg/kg inhibited the incorporation of (1-14C) acetate but not of (2-14C)mevalonate into liver sterols in normal rats.5)In rats with thoracic lymph-duct fistula which were fed a hypercholesterolemic diet, sd-YM-95831 did not modify intestinal absorption of (4-14C) cholesterol.6)In rats with bile-duct fistula which were intravenously given (4-14C) cholesterol labeled lipoproteins, sd-YM-95831 significantly increased the excretion of the radioactivity in bile. Also, sd-YM-95831 significantly increased the fecal excretion of acidic sterols derived from (4-14C)-cholesterol which was orally administered.7)In the partially hepatectomized rats which were fed a hypercholesterolemic diet, YM-95831 did not alter the level of serum TC and HDL-cholesterol (HDL-C). Whereas, YM-95831 decreased serum TC and increased serum HDL-C in rats with thoracic lymph-duct fistula.8)YM-95831 inhibited noncompetitively acylCoA : cholesterol acyltransferase with the inhibition constant of 2.8μM in the aorta from atherosclerotic rabbits.9)In the hypercholesterolemic monkeys, sd-YM-95831 significantly decreased serum TC and TG levels, and increased HDL-C levels. Also, sd-YM-95831 depressed the atherosclerotic lesions in dose-dependent manner and significantly decreased the content of esterified cholesterol in the aorta.These results indicate that the hypolipidemic effect of sd-YM-95831 is associated with the inhibition of cholesterol biosynthesis and the stimulation of the catabolic rate of cholesterol to bile acids, and a prophylactic application of the drug to atherosclerotic subjects seems possible." @default.
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- W2275455478 date "1984-01-01" @default.
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- W2275455478 doi "https://doi.org/10.1272/jnms1923.51.302" @default.
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