Hypolipidemic effects of NB-598 in dogs.
NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index.
Horie
M
M
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd, Tokyo, Japan.
Sawasaki
Y
Y
Fukuzumi
H
H
Watanabe
K
K
Iizuka
Y
Y
Tsuchiya
Y
Y
Kamei
T
T
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004285:Dogs; D005243:Feces / Q000737:chemistry; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010105:Oxygenases / Q000037:antagonists & inhibitors; D010743:Phospholipids / Q000097:blood; D019821:Simvastatin; D013185:Squalene / Q000097:blood / Q000378:metabolism; D050603:Squalene Monooxygenase; D013876:Thiophenes / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001596:Benzylamines; D001647:Bile Acids and Salts; D008055:Lipids; D008074:Lipoproteins; D010743:Phospholipids; D013876:Thiophenes; D014280:Triglycerides; C030104:lipoprotein cholesterol; C066059:NB 598; D013185:Squalene; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D010105:Oxygenases; D050603:Squalene Monooxygenase