Boehme C L, Strobel H W
Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77225, USA.
Neurotox Res. 2001 Aug;3(4):329-37. doi: 10.1007/BF03033194.
The metabolism of chlorpromazine by expressed recombinant cytochromes P450 4F4 and 4F5 cloned from rat brain was analyzed to characterize the individual activities of the isoforms. Both isoforms metabolized chlorpromazine to both the N-demethylated and the S-oxide products. When isoforms were incubated with chlorpromazine in the presence of increasing concentrations of imipramine, imipramine significantly inhibited both N-demethylation and S-oxidation of chlorpromazine. A dilution of the serum fraction of anti-4F antibody was also found to significantly inhibit both S-oxidation and N-demethylation of chlorpromazine by both 4F4 and 4F5.
为了表征细胞色素P450 4F4和4F5同工型的个体活性，分析了从大鼠脑中克隆的重组细胞色素P450 4F4和4F5对氯丙嗪的代谢情况。两种同工型均将氯丙嗪代谢为N-去甲基化产物和S-氧化物产物。当同工型与氯丙嗪在不同浓度的丙咪嗪存在下孵育时，丙咪嗪显著抑制氯丙嗪的N-去甲基化和S-氧化。还发现抗4F抗体血清部分的稀释液能显著抑制4F4和4F5对氯丙嗪的S-氧化和N-去甲基化。
