pactimibe has been researched along with Hypercholesterolemia* in 2 studies
2 other study(ies) available for pactimibe and Hypercholesterolemia
| Article | Year |
|---|---|
Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe.
Pactimibe sulfate, [7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate, a novel Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, was investigated in vitro and in vivo to characterize its potential. Pactimibe exhibited dual inhibition for ACAT1 and ACAT2 (concentrations inhibiting 50% [IC50s] at micromolar levels) more potently than avasimibe. Kinetic analysis revealed pactimibe is a noncompetitive inhibitor of oleoyl-CoA (Ki value: 5.6 microM). Furthermore, pactimibe markedly inhibited cholesteryl ester formation (IC50: 6.7 microM) in human monocyte-derived macrophages, and inhibited copper-induced oxidation of low density lipoprotein more potently than probucol. Pactimibe exerted potent lipid-lowering and anti-atherosclerotic effects in atherogenic diet-fed hamsters. At doses of 3 and 10 mg/kg for 90 days, pactimibe decreased serum total cholesterol by 70% and 72%, and aortic fatty streak area by 79% and 95%, respectively. Despite similar cholesterol lowering, fatty streak area reduction was greater by 10 mg/kg. These results suggest that ACAT1/2 dual inhibitor pactimibe has anti-atherosclerotic potential beyond its plasma cholesterol-lowering activity. Topics: Acyl Coenzyme A; Animals; Arteriosclerosis; Catalysis; Cell Line; Cell-Free System; Cholesterol Esters; Cricetinae; Diet, Atherogenic; Dose-Response Relationship, Drug; Humans; Hypercholesterolemia; Hypolipidemic Agents; Indoleacetic Acids; Lipids; Lipoproteins, LDL; Macrophages; Monocytes; Oxidation-Reduction; Phosphatidylcholine-Sterol O-Acyltransferase; Rabbits; Rats; Rats, Sprague-Dawley; Sterol O-Acyltransferase; Sterol O-Acyltransferase 2 | 2006 |
Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor.
Novel acyl-coenzyme A:cholesterol acyltransferase inhibitor pactimibe has been evaluated in vivo; it exhibited significant serum cholesterol lowering activities in hamsters and monkeys without affecting non-high density lipoprotein cholesterol levels. The mechanism of the hypocholesterolemic action of pactimibe was examined in normocholesterolemic hamsters in this study. Results with the dual-isotope plasma ratio method indicated that pactimibe inhibits cholesterol absorption from the intestine, reduces cholesteryl ester formation in the liver, and enhances its elimination from the body. The Triton WR-1339 experiment showed that pactimibe inhibited secretion of very low density lipoprotein cholesterol from the liver. These results suggest that pactimibe is likely to have multiple mechanisms of action responsible for its effectiveness in reducing serum cholesterol. Topics: Animals; Anticholesteremic Agents; Bile; Cholesterol; Cholesterol, VLDL; Cricetinae; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Feces; Hypercholesterolemia; Indoleacetic Acids; Intestinal Absorption; Liver; Macaca fascicularis; Male; Mesocricetus; Phospholipids; Postprandial Period; Rats; Rats, Sprague-Dawley; Sterol Esterase; Sterol O-Acyltransferase; Time Factors; Triglycerides | 2006 |