Inhibition of rat aorta semicarbazide-sensitive amine oxidase by 2-phenyl-3-haloallylamines and related compounds.
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 corresponding 3-chloroallylamines. These halogen-containing compounds were irreversible inhibitors of SSAO after preincubation with aorta homogenates; kinetic evidence for an initial competitive, reversible interaction (Ki around 0.4-0.6 microM) was found with two compounds (MDL 72145 and 72274). A similar Ki (approx. 0.7 microM) 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 H2O2 production from amine metabolism demonstrated that MDL 72200 was a substrate (Km = 1.4 microM) for SSAO, with a Vmax approximately five times smaller than that of benzylamine (Km = 8.1 microM). Of particular interest in this study is the finding 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.
D000498:Allyl Compounds / Q000494:pharmacology*; D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing); D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000201:enzymology; D007700:Kinetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000498:Allyl Compounds; D000588:Amines; C090015:MDL 72274A; D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; D000499:Allylamine; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors