In-vivo effects of (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine (MDL 72145) on amine oxidase activities in the rat. Selective inhibition of semicarbazide-sensitive amine oxidase in vascular and brown adipose tissues.
One hour after MDL 72145 ((E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine) (2.5 mg kg-1) was given by intraperitoneal injection, the semicarbazide-sensitive amine oxidase (SSAO) activity of rat aorta and brown adipose tissue measured in-vitro was reduced by more than 95% of its control value, whereas the monoamine oxidase (MAO-A) activity remained virtually unaffected. The action of this drug on amine oxidases in the liver at this dose was less selective. The in-vitro effect of MDL 72145 on the soluble enzyme diamine oxidase from rat intestine was 100 fold less potent than that of semicarbazide but about equipotent with semicarbazide on sheep plasma amine oxidase. Overall MDL 72145 was selectively more active against membrane bound SSAO enzymes that deaminate primary monoamines. Although MDL 72145 does inhibit MAO-B activity these results suggest that this compound may be used to study the effect of selective inhibition of SSAO activity on the pharmacological responses of appropriate preparations in-vitro.
Elliott
J
J
Department of Pharmacology, University of Cambridge, UK.
Callingham
B A
BA
Barrand
M A
MA
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology*; D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D012663:Semicarbazides / Q000494:pharmacology*; D012756:Sheep; D013997:Time Factors
D000588:Amines; D008996:Monoamine Oxidase Inhibitors; D012663:Semicarbazides; D000499:Allylamine; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D008995:Monoamine Oxidase