The present paper aims to investigate whether p-amino-2′,4′-dichlorodiphenyl ether and p-amino-4′-methyldiphenyl ether are inhibitors as well as inducers of P450. Mice were given daily intraperitoneal (ip) injections of p-amino-2′,4′-dichlorodiphenyl
ether (0.25 mmol/kg) or p-amino-4′-methyldiphenyl ether (0.25 mmol/kg) for 4 days and tested at 24 h and 48 h after the last dose injection. The results showed the mice pentobarbital sleeping time was shorter and the P450 content of hepatic microsome increased significantly in
the group pretreated with p-amino-4′-methyldiphenyl ether when compared with the control group, while in mice pretreated with p-amino-2′,4′-dichlorodiphenyl ether the hepatic microsome P450 content increased but the pentobarbital sleeping time was extended in
clear contrast to the control group. The sleeping time of the phenobarbital group (80 mg/kg daily ip injection for 4 days) was shortened at 24 h after the last injection with increased P450 content of hepatic microsome, but it showed no difference at 48 h. The zoxazolamine-paralysis times
of mice treated with p-amino-2′,4′-dichlorodiphenyl ether were longer than those of the control mice, while the same dose of zoxazolamine did not lead to paralysis in mice pretreated with BNF. p-amino-2′,4′-dichlorodiphenyl ether and p-amino-4′-methyldiphenyl
ether inhibited the activity of 7-ethoxyresorufin O-deethylase from rat hepatic microsome induced by BNF in vitro by 70.0% and 50.1% respectively. These results suggest that p-amino-2′,4′-dichlorodiphenyl ether and p-amino-4′-methyldiphenyl
ether are inhibitors as well as inducers of P450.
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Document Type: Research Article
College of Pharmaceutical Sciences, Zhejiang University, 353 Yan'an Road, Hangzhou Zhejiang, 310031, China, Email: [email protected]
Department of Chemistry, Zhejiang University, Hangzhou Zhejiang, China
Publication date: September 1, 2003
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