Inhibition of a type B monoamine oxidase inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine (MDL-72974A), on semicarbazide-sensitive amine oxidases isolated from vascular tissues and sera of different species.
(E)-2-(4-Fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A) has been discovered recently to be a very potent and highly selective type B monoamine oxidase inhibitor. We have found that this inhibitor is also capable of inhibiting semicarbazide-sensitive amine oxidases (SSAOs) obtained from vascular tissues and sera of different species. The inhibition of SSAO by MDL-72974A was irreversible and time dependent. It was competitive without preincubation of the enzyme with the inhibitor and demonstrated a mixed-type of inhibition when the enzyme was preincubated with the inhibitor. The IC50 values were estimated to be 2 x 10(-9) M, 5 x 10(-9) M, 8 x 10(-8) M and 2 x 10(-8) M for SSAO from dog aorta, rat aorta, bovine aorta and human umbilical artery, respectively. SSAO obtained from bovine serum was relatively insensitive to MDL-72974A (IC50 = 3 x 10(-7) M. Following intraperitoneal administration of MDL-72974A, rat brain MAO-B was inhibited with the ED50 value being about 0.2 mg/kg. Rat aorta SSAO was also inhibited and to a similar extent by the same dose. MDL-72974A is the most potent SSAO inhibitor that has been described thus far.
Yu
P H
PH
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Zuo
D M
DM
D000498:Allyl Compounds; D000594:Amino Acid Oxidoreductases / Q000097:blood / Q000187:drug effects / Q000302:isolation & purification*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002082:Butylamines / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D002421:Caudate Nucleus / Q000187:drug effects / Q000201:enzymology; D003641:Deamination; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000097:blood; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000201:enzymology
D000498:Allyl Compounds; D002082:Butylamines; D008996:Monoamine Oxidase Inhibitors; D012663:Semicarbazides; C058000:mofegiline; D000594:Amino Acid Oxidoreductases; D008995:Monoamine Oxidase