Antihypercholesterolemics

Simvastatin is a semi-synthetic statin that is produced from the natural statin lovasta-tin7 Both are potent antihypercholesterolemic agents with simvastatin differing from lovastatin by just one additional methyl substituent residing on the 2-(5)-methylbutyrate side chain (Figure 1.6). 

Atorvastatin, an antihypercholesterolemic agent, is a synthetic drug that was initially produced in kilogram quantities using an 11-step chemical route. The iy -l,3-diol-con-taining side chain was produced from the chiral starting material, isoascorbic acid (Scheme 1.25). ... 

Antihypercholesterolemic activity. Gum, administered to female rats at a concentra-... 

Antigalactogogue effect. Dried kernel, administered to cows at a concentration of 50% of diet, was inactive . Antihypercholesterolemic activity. Seeds, administered orally to 20 adults with mild hypercholesterolemia at a dose of 5.1 g/day for 40 days, reduced LDL cholesterol by 8% and total cholesterol by 6% . Dried seed fiber, in the ration of Syrian hamster at a dose of 7.5% of diet, was active . Dried seed fiber, administered orally to adults at a dose of 10.2 g/day, was active . Dried seed fiber, administered orally to 50 healthy children 2 to 11 years of age at a dose of 6.4 g/ day for 12 weeks, was active The hydro-phobic colloid of the dried seed, administered in the ration of sea quails at a dose of 10% of diet, was active vs diet-inducing hypercholesterolemia . The seed hull, administered in the ration of genetically diabetic mice at a dose of 2.5% of diet for 18 weeks, was active. Total cholesterol was lower, and HDL-cholesterol higher in psyllium-fed than in placebo-fed animals . The seed hull, administered orally to 286... 

Antihypercholesterolemic effect. Polico-sanol, administered orally to normocholes-terolemic New Zealand rabbits at doses of 5-200 mg/kg for 4 weeks, significantly reduced total cholesterol and low-density lipoprotein cholesterol (LDL-C) serum levels in a dose-dependent manner. Serum triglyceride (TC) levels of the treated and control animals were significantly different, but the reduction observed was not dose-dependent. High-density lipoprotein cholesterol (HDL-C) levels remained unchanged. The results indicated that the reduction in total cholesterol values induced by policosanol was mainly mediated through a decrease in LDL-C levels . Policosanol was administered to patients who were obese (body mass... 

Antihypercholesterolemic activity. Oleo-resin, administered orally to rats, was active vs cholesterol-primed animals . Ethanol (95%) extract of the dried rhizome, administered intragastrically to male rabbits at a dose of 200 mg/kg, was active vs cholesterol-fed animals ° °h... 

Marketed as the antihypercholesterolemic drug, Mevacor. (The closely related statin, Zocor, is produced from lovastatin by replacing the 2-methylbutanoic acid side chain with the 2, 2-dimethylbutanoic acid side chain). 

Inhibitors of squalene synthase have recently received considerable attention in the search for new antihypercholesterolemic agents. BP-based inhibitors were designed as mime tics of the putative carbocation intermediate formed from FPP in the initial step of the squalene synthase reaction. (See also mechanism of action of nitrogen-containing BPs and Fig. 15.5.) The BP function served as a stable surrogate for the pyrophosphate moiety [27]. 

Of 18 ISQ analogs tested, compound 42 was the most potent inhibitor of cholesterol biosynthesis showing 50.4 % inhibition of the total cholesterol biosynthesis and an IC50 value of l.lxlO M at squalene synthase (SQS) indicating antihypercholesterolemic potential [39]. Compound 42 and some derivatives are under further investigation for their clinical usefulness. In designing these compounds, the precedence... 

HMGRI and additional antihypercholesterolemic agent Lovastatin/niacin (Advicor) Simvastatin/ezetimibe (Vytorin)... 

Significant reduction in serum cholesterol levels can also be demonstrated in animals simultaneously fed polyenes and high sterol diets. Dogs appeared more able to maintain their serum cholesterol levels when fed sterols and filipin, amphotericin B or candicidin [145,535] but nystatin had no effect. The anti-hypercholesterolemic effect was not simply due to the prevention of sterol uptake [538,539]. A consequence of the excretion of sterol-polyene complexes in the faeces is the loss of bile salts (which are steroids) and this tends to remove sterol from the body. This resulted in increased hepatic synthesis, increased utilization of adipose fat and reduced sebum levels. Candicidin has been suggested as an antihypercholesterolemic agent in man [546]. 

C18H30O2 M 278.434 (Z,Z,Z) form [506-26-3] y-Linolenic acid. Gamolenic acid, ban, usan Isol. from evening primrose seed oil. A minor component of many animal lipids. Antihypercholesterolemic drug. Hexabromide Mp 196 dec. 

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