Tsujita Y, Kuroda M, Tanzawa K, Kitano N, Endo A
Atherosclerosis. 1979 Mar;32(3):307-13. doi: 10.1016/0021-9150(79)90174-6.
ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, significantly reduced both serum cholesterol and phospholipid levels in dogs, when used at a dosage higher than 10 mg/kg per day. Triglyceride levels were not consistently changed, but beta- and pre-beta-lipoproteins were preferentially reduced. Serum cholesterol levels were reduced by 44--45% at the higher dosage of 100--400 mg/kg per day (for 5 weeks) but ML-236B caused no significant changes in the cholesterol content of the liver and aorta and in the activities of serum GOT, GPT, CPK and lecithin : cholesterol acyltransferase. Fecal excretion of neutral sterols was unaffected but that of bile acids was markedly elevated by the drug. Under these conditions, hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, showed no detectable changes.
ML - 236B是3 - 羟基 - 3 - 甲基戊二酰辅酶A还原酶的竞争性抑制剂，当以高于每天10毫克/千克的剂量用于犬类时，可显著降低犬的血清胆固醇和磷脂水平。甘油三酯水平没有持续变化，但β - 脂蛋白和前β - 脂蛋白优先减少。在每天100 - 400毫克/千克的较高剂量下（持续5周），血清胆固醇水平降低了44% - 45%，但ML - 236B对肝脏和主动脉的胆固醇含量以及血清谷草转氨酶、谷丙转氨酶、肌酸磷酸激酶和卵磷脂：胆固醇酰基转移酶的活性没有显著影响。中性固醇的粪便排泄不受影响，但该药物可使胆汁酸的粪便排泄显著增加。在这些条件下，胆汁酸生物合成中的限速酶——肝胆固醇7α - 羟化酶没有可检测到的变化。
