Cholesterol agents that lower

Saponins. Although the hypocholesterolemic activity of saponins has been known since the 1950s, thek low potency and difficult purification sparked Htde interest in natural saponins as hypolipidemic agents. Synthetic steroids (292, 293) that are structurally related to saponins have been shown to lower plasma cholesterol in a variety of different species (252). Steroid (292) is designated CP-88,818 [99759-19-0]. The hypocholesterolemic agent CP-148,623 [150332-35-7] (293) is not absorbed into the systemic ckculation and does not inhibit enzymes involved in cholesterol synthesis, release, or uptake. Rather, (293) specifically inhibits cholesterol absorption into the intestinal mucosa (253). As of late 1996, CP-148,623 is in clinical trials as an agent that lowers blood concentrations of cholesterol (254). 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

The recent years have seen the success of statins like Lipitor (atorvastatin) as hypolipidemic agents that help treating cardiovascular disease primarily by lowering low-density lipoproteins ( bad cholesterol ) levels. Another novel strategy is to tackle the same problem by elevating high-density lipoproteins (H D L or good cholesterol ) levels via inhibition of cholesteryl ester transfer protein (CETP). 

The therapeutic class that uniquely exemplifies lactone prodrugs are the statins, i.e., the cholesterol-lowering agents that act by inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34). This microsomal enzyme catalyzes conversion of HMG-CoA to mevalonate, an important rate-limiting step in cholesterol biosynthesis. Cholesterol synthesis occurs mainly... 

Endo A. (1985) Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. J Med Chem 28 401 05. 

Nicotinic acid is an antilipidemic agent that effectively reduces serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and triglycerides, and increases concentrations of high-density lipoprotein (HDL) cholesterol. It has been suggested that the marked lowering of serum cholesterol seen during treatment of dyslipidemia with nicotinic acid results from hepatotoxi-city (1). 

Patel SB. Ezetimibe a novel cholesterol-lowering agent that highlights novel physiologic pathways. 

These antihyperlipidemic agents inhibit de novo cholesterol synthesis, and deplete the intracellular supply of cholesterol. This prompts the cell to increase the number of specific cell-surface LDL receptors that can bind and internalize circulating LDLs. Thus the end result is a reduction in plasma cholesterol, both by lowered cholesterol synthesis and by increased catabolism of LDL. 

Statins are cholesterol-lowering agents that reversibly inhibit HMG-CoA reductase, which catalyzes a rate-limiting... 

Fluvastatin, a cholesterol-lowering agent that inhibits hydroxy-methylglutaryl-coenzyme A (MHG-CoA) reductase, is effective in the reduction of low-density lipoprotein and total cholesterol levels in patients with primary hypercholesterolemia (types Ila and Ilb) when response to diet and other nonpharmacologic measures have been inadequate (see also Figure 35). 

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