SPECIES-DIFFERENCES IN THE METABOLISM AND MACROMOLECULAR BINDING OF METHAPYRILENE - A COMPARISON OF RAT, MOUSE AND HAMSTER

被引：12

作者：

LAMPE, MA

KAMMERER, RC

机构：

[1] UNIV CALIF LOS ANGELES,SCH MED,DEPT PHARMACOL,LOS ANGELES,CA 90024

[2] UNIV CALIF LOS ANGELES,SCH MED,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024

来源：

XENOBIOTICA | 1990年 / 20卷 / 12期

关键词：

D O I：

10.3109/00498259009046626

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The metabolism of methapyrilene (MPH) by rat, hamster and mouse liver microsomes in vitro was investigated together with the binding of 14C-MPH to calf thymus DNA after metabolic activation. 2. Both quantitative and qualitative differences in MPH metabolism were observed in these three species. Mouse liver microsomes catalyse the formation of two novel isomers of hydroxypyridylmethapyrilene (hydroxypyridyl-MPH) as determined by mass spectral analysis. N,N'-Didesmethylmethapyrilene (didesmethyl-MPH) was formed in detectable quantities only when hamster liver microsomes were used. 3. Incubation of liver microsomes from all three species catalysed the binding of 14C-MPH to exogenous DNA, which was quantitatively similar for all three species. The effect of the cytochrome P-450 inhibitor, 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), and methimazole, a flavin-dependent monooxygenase inhibitor, on binding differed significantly for the three species studied. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：1269 / 1280

页数：12

共 34 条

[1] THE EFFECTS OF METHAPYRILENE HYDROCHLORIDE ON HEPATOCARCINOGENICITY AND PENTOBARBITAL-INDUCED SLEEPING TIME IN RATS AND MICE [J].