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- W1982186937 abstract "YM-16638 was found in preclinical studies to be an orally active leukotriene antagonist. Because LY-171883, another leukotriene receptor antagonist with a similar structure to YM-16638, showed a triglyceride-lowering effect with a peroxisomal proliferative effect in monkeys fed a normal diet, we investigated whether YM-16638 also showed a serum triglyceride-lowering effect by examining serum and hepatic lipid levels in cynomolgus monkeys fed a normal diet supplemented with YM-16638 for 4 weeks at a daily dose of 3.75 mg (8.5 μmole), 30 mg (67.7 μmole) or 60 mg (135.4 μmole)/kg body weight. Monkeys given YM-16638 showed a dose-dependent decrease in serum total cholesterol. At 2 weeks of treatment, serum LDL- and HDL-cholesterol in the YM-16638 group showed marked decreases of 35% and 32%, respectively. However, serum triglyceride levels did not change. By contrast, hepatic cholesterol and cholesterol ester levels in this group were only slightly increased, without any effect on hepatic triglyceride level. In vitro investigation of the effect of YM-16638 on LDL-receptor activity and mRNA expression in the human hepatoma cell line HepG2 cells showed that YM-16638 increased LDL-receptor activity in a dose-dependent manner at 44 h of treatment. mRNA level in these cells was also increased 1.7-fold at 8 h of treatment. These results suggest that the decrease in serum cholesterol level in monkeys treated with YM-16638 may be due to an increase in hepatic LDL-receptor activity. Furthermore, they suggest that YM-16638 may represent a potent hypocholesterolemic drug without serious side effects. © 1996 Wiley-Liss, Inc." @default.
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- W1982186937 date "1996-06-01" @default.
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- W1982186937 title "Cholesterol-lowering effect of YM-16638 in cynomolgus monkeys" @default.
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- W1982186937 doi "https://doi.org/10.1002/(sici)1098-2299(199606)38:2<86::aid-ddr2>3.0.co;2-g" @default.
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