McGraw N P, Castagnoli N
J Med Chem. 1981 Mar;24(3):299-304. doi: 10.1021/jm00135a012.
The stereoselective pharmacological behavior and metabolism of the potent psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane have led to an investigation of the interactions of the racemic amine, its enantiomers, and the corresponding N-hydroxy metabolites with rabbit liver microsomal cytochrome P-450. An examination of the formation of cytochrome P-450 metabolic intermediate complexes with these species suggests that N-oxidation of the pharmacologically active (R)-amine in inhibited by the S enantiomer. Additionally, metabolic intermediate complex formation [favored by the (R)-amine] appears to be associated with loss of microsomal mixed function N-oxidase activity. The results have led to the prediction that N-hydroxylation of pure (R)-amine may be a qualitatively more important pathway than that observed with racemic amine even though this biotransformation may be suicidal.
强效拟精神病胺1-(2,5-二甲氧基-4-甲基苯基)-2-氨基丙烷的立体选择性药理行为和代谢情况，促使人们对消旋胺、其对映体以及相应的N-羟基代谢物与兔肝微粒体细胞色素P-450之间的相互作用展开研究。对这些物质与细胞色素P-450代谢中间复合物形成情况的检查表明，药理活性(R)-胺的N-氧化受到S对映体的抑制。此外，代谢中间复合物的形成[受(R)-胺青睐]似乎与微粒体混合功能N-氧化酶活性的丧失有关。这些结果预测，即使这种生物转化可能具有自杀性，但纯(R)-胺的N-羟基化在性质上可能是比消旋胺更为重要的途径。
