Inhibition of rat aorta semicarbazide-sensitive amine oxidase by 2-phenyl-3-haloallylamines and related compounds

Abstract

The inhibition of semicarbazide-sensitive amine oxidase (SSAO) in rat aorta homogenates by some 2-phenyl-3-haloallylamines has been studied. Derivatives containing a fluorine atom were approximately three times more potent than the corresponcling 3-chloroallylamines. These halogencontaining compounds were irreversible inhibitors of SSAO after preincubation with aorta homogenates; kinetic evidence for an initial competitive, reversible interaction ( K i, around 0.4–0.6 μM) was found with two compounds (MDL 72145 and 72274). A similar K i (approx. 0.7 μM) was obtained with 2-phenylallylamine (MDL 72200). However, this compound which lacks a halogen atom was a reversible inhibitor, even after preincubation. The use of a spectrophotometric assay to measure H 2O 2 production from amine metabolism demonstrated that MDL 72200 was a substrate ( K m = 1.4 μM) for SSAO, with a V max. approximately five times smaller than that of benzylamine ( K m = 8.1 μM). Of particular interest in this study is the fincling that (E)-2-phenyl-3-chloroallylamine (MDL 72274) is highly selective as an inhibitor of SSAO, compared with MAO-A or B activities, and may be a useful compound for investigating the importance of SSAO in animal tissues.