Summary
Lovastatin and simvastatin are potent competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Key inhibit the synthesis of cholesterol in cultured HepG23 cells, rat hepatocytes and in rats. The primary target organ of cholesterol synthesis inhibition by lovastatin and simvastatin is the liver. Lovastating and simvastatin lower levels of plasma cholesterol in rats, dogs and rabbits by inhibition the endogenous cholesterol synthesis and induction of LDL receptor in the liver.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Lipid Research Clinics Program (1984) The Lipid Research Clinics Coronary Primary Prevention Trial Results: I. Reduction in incidence of coronary heart disease; II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 251: 351–374
Turley SD, Dietschy JM (1982) Arias I, Popper H, Schachter D, Shafritz DA (eds) In: The liver: biology and pathobiology. Raven Press, New York, pp 467–492
Tsuijita Y, Kuroda M, Shimada Y, Tanzawa K, Arai M, Kaneko I, Tanaka M, Masuda H, Tarumi C, Watanabe Y (1986) CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta 887: 50–60
Saito Y, Shiki Y, Shirai K, Yoshida S (1988) Effect of a new synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on cholesterol synthesis and low density lipoprotein uptake by primary cultures of rat hepatocytes. Arzneimittel-Forsch/Drug Res 38: 251–253
Germershausen JI, Hunt VM, Bostedor RG, Bailey PJ, Karkas JD, Alberts AW (1989) Tissue selectivity of the cholesterol-lowering agents lovastatin, simvastatin and pravastatin in rats in vivo. Biochem Biophys Res Commun 158: 667–675
MacDonald JS, Gerson RJ, Kornbrust DJ, Kloss MW, Prahalada S, Berry PH, Alberts AW, Bokelman DL (1988) Preclinical evaluation of lovastatin. Am J Cardiol 62: 16J27J
Chaho Y-S, Yamin T-T, Seidenberg J, Kroon PA (1986) Secretion of cholesteryl-ester-rich lipoproteins by the perfused livers of rabbits fed a wheat-starch-casein diet. Biochim Biophys Acta 876: 392–398
Chao Y-S, Kroon PA, Yamin TT, Thompson GM, Alberts AW (1983) Regulation of receptor-dependent degradation of LDL by mevinolin in rabbits with hypercholesterolemia induced by a wheat starch-casein diet. Biochim Biophys Acta 754: 134–141
Kroon PA, Hand KM, Huff JW, Alberts AW (1982) The effects of mevinolin on serum cholesterol levels of rabbits with endogenous hypercholesterolemia. Atherosclerosis 44: 41–48
Kovanen PT, Bilheimer DW, Goldstein JL, Jaramillo JJ, Brown MS (1981) Regulatory role of hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci USA 78: 1194–1198
Ma PTS, Gil G, Südhof TC, Bilheimer DW, Goldstein JL, Brown MS (1986) Mevinolin, and inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. Proc Natl Acad Sci USA 83: 8370–8374
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chao, Y., Chen, J.S., Hunt, V.M. et al. Lowering of plasma cholesterol levels in animals by lovastatin and simvastatin. Eur J Clin Pharmacol 40 (Suppl 1), S11–S14 (1991). https://doi.org/10.1007/BF03216281
Issue Date:
DOI: https://doi.org/10.1007/BF03216281