Bast A, Savenije-Chapel E M, Noordhoek J
J Pharm Sci. 1984 Jul;73(7):953-6. doi: 10.1002/jps.2600730723.
Complexation of ferrous cytochrome P450 by metabolic intermediates formed during NADPH-catalyzed metabolism of compounds structurally related to orphenadrine was studied. This so-called metabolic intermediate complexation was determined in rat liver microsomes, obtained from phenobarbital-pretreated rats, at 455 nm using 33 microM of the orphenadrine derivatives. Using secondary amine derivatives with various N-alkyl substituents, a parabolic relationship between the logarithm of percentage of cytochrome P450 complexation and hydrophobic fragmental constant was observed. The derivative with a bulky tertiary butyl group, however, was devoid of metabolic intermediate-complexing activity. This indicates that steric factors besides lipid solubility may govern the complexing activity; also substitution at the phenyl group affects metabolic intermediate complex formation.
研究了在NADPH催化的与邻苯海拉明结构相关的化合物代谢过程中形成的代谢中间体与亚铁细胞色素P450的络合作用。在从苯巴比妥预处理的大鼠获得的大鼠肝微粒体中，使用33μM的邻苯海拉明衍生物在455nm处测定这种所谓的代谢中间体络合作用。使用具有各种N-烷基取代基的仲胺衍生物，观察到细胞色素P450络合百分比的对数与疏水片段常数之间呈抛物线关系。然而，具有庞大叔丁基的衍生物没有代谢中间体络合活性。这表明除脂溶性外，空间因素可能控制络合活性；苯基上的取代也会影响代谢中间体络合物的形成。
