Hydroxymethylglutaryl-coenzyme A reductase inhibitors

Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme a reductase inhibitors. Am J Health Syst Pharm 1995 52(15) 1639 15. 

Landesman KA, Stozek M, Freeman NJ. Rhabdomyolysis associated with the combined use of hydroxymethylglutaryl-coenzyme A reductase inhibitors with gemfibrozil and macrolide antibiotics. Conn Med 1999 63(8) 455-7. 

Jamal SM, EisenbergMJ, Christopoulos S. Rhab-domyolysis associated with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am Heart J. 2004 147 956-965. 

Rueckschloss U, Galle I, Holtz J, Zerkowski HR, Morawietz H. Induction of NAD(P)H oxidase hy oxidized low-density lipoprotein in human endothelial cells antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 2001 104 1767-1772. 

P.-T. Ho and S. Chung, Synthesis of 2,4-dideoxy-D-eryi/tro-hexopyranose. An intermediate for synthesis of the lactone moiety of inhibitors of hydroxymethylglutaryl-coenzyme A reductase, Carbohydr. Res., 125 (1984) 318-322. 

Alberts, A.W., Chen, J., Kuron, G., Hunt, V., Huff, J., Hoffman, C., Rothrock, J., Lopez, M., Joshua, H., Harris, E., Patchett, A., Monaghan, R., et al. (1980). Mevinolin a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 77 3957-3961. 

Mevinolin and compactin. An example of reversible ring closure is found with mevinolin and compactin, which are both potent inhibitors of hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-determining enzyme in the de novo biosynthesis of cholesterol. In vivo these ring-closed derivatives (Fig. 14.8) are hydrolysed to... 

The discovery of compactin (29a) 63, 64) and mevinolin (29b) (Figure 4) (65) two decades ago as inhibitors of hydroxymethylglutaryl coenzyme A reductase revolutionized research toward the u eatment of hypercholesterolemia. During this period several analogs of mevinolin and compactin, popularly known as statin drugs, have been examined, approved and marketed as cholesterol lowering pharmaceuticals (66). 

Alberts AW, Chen J, Kuron G, et al. 1980. Mevinolin a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and cholesterol-lowering agent. Proc Natl Acad Sci USA - Biological Sciences 77(7) 3957-3961. 

C. R. Sirtori, Tissue Selectivity of Hydroxymethylglutaryl Coenzyme A (HMG CoA) Reductase Inhibitors , Pharmacol. Ther. 1993, 60, 431-459. 

M. J. Kaufman, Applications of oxygen polarography to drug stability testing and formulation development Solution-phase oxidation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, Pharm. Res. 7, 289-292(1990). 

The hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, otherwise known as the statins, have been found to increase bone formation via enhanced activity of the bone morphogenic protein 2 (BMP-2) gene. This gene increases osteoblast differentiation. In addition, by inhibiting HMG-CoA reductase, the statins not only prevent the biosynthesis of cholesterol but also prevent the formation of compounds associated with osteoclast activation (45). Unfortunately, clinical data... 

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