苯氟雷司及其主要代谢产物对大鼠肝微粒体膜性质的体外影响。

In vitro influence of benfluorex and its main metabolites on rat liver microsomal membrane properties.

作者信息

Orsière T, Chauvet M, Dell'Amico M, Lafont H, Bourdeaux M

机构信息

Equipe Protéines Membranaires (GRIPP), UFR de Pharmacie, Marseille, France.

出版信息

Chem Biol Interact. 1995 Aug 18;97(3):297-306. doi: 10.1016/0009-2797(95)03624-u.

DOI:10.1016/0009-2797(95)03624-u

PMID:7671345

Abstract

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.

摘要

已表明，在30微摩尔浓度下，苯氟雷司及其三种主要代谢产物可抑制大鼠肝微粒体制剂中的酰基辅酶A胆固醇酰基转移酶活性，并使这些膜发生脂膜微团化，这可通过脂质序参数的降低反映出来。当药物浓度较高（60 - 200微摩尔）时，这些化合物在酶抑制特性上有所不同，但保持相同的脂膜微团化作用。只有母体化合物具有剂量依赖性抑制作用。结合化合物的化学性质，特别是它们的电荷和亲脂特性对这些结果进行了讨论。