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浙江大学学报（医学版）
浙江大学学报（医学版）  1994, Vol. 23 Issue (3): 102-105    DOI: 10.3785/j.issn.1008-9292.1994.03.002
论著     
对氨基二苯醚类对细胞色素P-450抑制机理的探讨
蒋惠娣1, 刘志强2
1. 浙江医科大学无机化学教研室;
2. 浙江医科大学药物分析教研室
INVESTIGATION OF MECHANISM OF INHIBITORY EFFECT OF P-AMINO-DIPHENYL ETHERS ON CYTOCHROME P-450
Jiang Huidi1, Liu Zhiqiang2
Department of Pharmacy, Zhejiang Medical University
 全文: PDF(292 KB)   HTML ( ) 
摘要： 本文研究发现,体内抑制细胞色素P-450活性强、中、弱的三个对氨基二苯醚同系物——4-个氨基-2',4'-二氯二苯醚、4-氨基-4'-氯二苯醚、4-氨基-2',3'-二甲基二苯醚与苯巴比妥诱导的大鼠肝微粒体在NADPH及O2存在下,于37℃经或未经预孵育(5min),对P-450对硝基茴香醚脱甲基酶均呈竞争性抑制。预孵育后三者Ki值(x±s)依次为0.113±0.096、0.363±0.263、0.703±0.244μmol/L。三者间差异显著(P<0.05)。三者Ki值与体内抑制P-450的能力呈负相关。若未经预孵育,三者Ki无明显差异。本实验还发现,三者体外形成的P-450-MI络合物可以解离。因此,本实验结果似提示,对氨基二苯醚类对P-450的抑制机理不同于传统的"准不可逆"抑制剂。
关键词： 对氨基二苯醚类;  细胞色素P-450类/拮抗剂和抑制剂;  硝基茴香醚邻-脱甲基酶类    
Abstract: This study reports that after preincubation of phenobarbital induced rat hepatic microsome with NADPH and O2 at 37℃ for 5 minute or without preincubation,4-amino-diphenyl ethers-4amino-2',4'-dichloro-diphenyl ether, 4-amino-4'-chloro-diphenyl ether and 4-amino-2',3'-dimethyl-diphenyl ether competitively inhibited the activity of p-nitro-anisole O-demethylase.It was calculated, after preincubation, the Ki values were 0.113±0.096,0.363±0.263 and 0.703±0.244μmol/L (x±s)respectively with significant difference among them (P<0.05).The Ki values were found to be consistent with the ability of compounds to inhibit the activity of P-450 in vivo. In the case without preincubation no significant difference was found among the Ki values. The authors also found cytochrome P-450 metabolic intermediate (MI) complex of the compounds could dissociate in vitro. The results indicate that the mechanism of p-amino-diphenyl ether to inhibit cytochrome P-450 is different from that of the classic pseudo-irreverse inhibitor.
Key words: P-amino-diphenyl ether    Cytochrome P-450/antag    Nitroanisole O-demethylase
收稿日期: 1993-02-25 出版日期: 1994-05-25
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蒋惠娣
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引用本文:

蒋惠娣, 刘志强. 对氨基二苯醚类对细胞色素P-450抑制机理的探讨[J]. 浙江大学学报（医学版）, 1994, 23(3): 102-105.

Jiang Huidi, Liu Zhiqiang. INVESTIGATION OF MECHANISM OF INHIBITORY EFFECT OF P-AMINO-DIPHENYL ETHERS ON CYTOCHROME P-450. Journal of ZheJiang University(Medical Science), 1994, 23(3): 102-105.

链接本文:

https://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.1994.03.002    或    https://www.zjujournals.com/med/CN/Y1994/V23/I3/102

[1] 李士敏, 刘志强, 俞滢. 柱切换高效液相色谱法测定小鼠肝脏对氨基二苯醚类化合物含量[J]. 浙江大学学报（医学版）, 1994, 23(5): 200-202.
[2] 傅旭春, 刘志强. 取代苯胺形成P-450-MI络合物构效关系的MINDO/3法研究[J]. 浙江大学学报（医学版）, 1993, 22(1): 16-18.