MECHANISM OF MONOAMINE OXIDASE-A INHIBITION BY BW-1370U87

被引：23

作者：

WHITE, HL

SCATES, PW

机构：

[1] Division of Pharmacology, The Wellcome Research Laboratories, North Carolina, Research Triangle Park

来源：

DRUG DEVELOPMENT RESEARCH | 1992年 / 25卷 / 03期

关键词：

ENZYME KINETICS; COMPETITIVE INHIBITION; ANTIDEPRESSANT; TYRAMINE; SEROTONIN; DIALYSIS;

D O I：

10.1002/ddr.430250303

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

BW 1370U87 is a potent, selective inhibitor of rat and human brain MAO-A with a competitive mechanism of action. K(i) = 0.01-mu-M with either serotonin or tyramine as substrate. After preincubation of BW 1370U87 with mitochondrial MAO, full enzyme activity was restored by dialysis. Following oral administration to rats, BW 1370U87 inhibited brain MAO-A in a dose-dependent manner, with a duration greater than 6 hr, but less than 24 hr. No significant inhibition of MAO-B by BW 1370U87 was observed either in vitro or ex vivo. The selectivity, reversibility, and competitive kinetics of the inhibition by BW 1370U87 may contribute to an improved safety profile with this novel MAO-A inhibitor.

引用

页码：191 / 199

页数：9

共 25 条

[1] CDNA CLONING OF HUMAN-LIVER MONOAMINE OXIDASE-A AND OXIDASE-B - MOLECULAR-BASIS OF DIFFERENCES IN ENZYMATIC-PROPERTIES [J].