In vitro influence of benfluorex and its main metabolites on rat liver microsomal membrane properties.
Benfluorex and its three main metabolites at 30 microM have been shown to inhibit Acyl CoA cholesterol acyl transferase activity in rat liver microsome preparations and to fluidize these membranes, as reflected by a decrease in the lipid order parameter. When drug concentrations were higher (60-200 microM), the compounds differed in their enzymatic inhibition properties but retained the same fluidizing effects. Only the parent compound had a dose-dependent inhibiting effect. These results are discussed with regard to the chemical properties of compounds, in particular their electric charges and their lipophilic characters.
Orsière
T
T
Equipe Protéines Membranaires (GRIPP), UFR de Pharmacie, Marseille, France.
Chauvet
M
M
Dell'Amico
M
M
Lafont
H
H
Bourdeaux
M
M
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002788:Cholesterol Esters / Q000378:metabolism; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005456:Fluorescent Dyes; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D001565:Benzoates; D002788:Cholesterol Esters; D005456:Fluorescent Dyes; D000960:Hypolipidemic Agents; D005277:Fenfluramine; C001584:benfluorex; C095600:1-(3-trifluoromethylphenyl)-2-(2-carboxymethyl)aminopropane; C073864:1-(3-trifluoromethylphenyl)-2-(N-(2-hydroxyethyl)amino)propane; D019817:Benzoic Acid; D002785:Sterol O-Acyltransferase