Monoamine oxidase inhibition by N-alkyloxycarbonyl derivatives of ethylene diamine.
Urethane type derivatives of ethylene diamine (EDA) were synthesized and tested as inhibitors of rat liver mitochondrial monoamine oxidase (MAO) A and B. The nature of the aromatic ring and the position of substituents in it were crucial for manifestation of the inhibitory activity. 3,4- and 2,4-Chlorobenzyloxycarbonyl-EDA derivatives were the most potent MAO A inhibitors. The inhibition of both MAO A and to a lesser extent MAO B depended on preincubation time with these inhibitors. The activity of both enzymes did not recover completely after repeated sedimentation and resuspension of inhibitor-treated mitochondria. The data suggest that these compounds exhibit properties of tight-binding reversible inhibitors of MAO A and B. The development of a new generation of MAO inhibitors causing simultaneous reversible nonselective inhibition of MAO A and B must meet one important criterion, the same type of inhibition of both the enzymes.
Pozdnev
V F
VF
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119832, Russia.
Axenova
L N
LN
Medvedev
A E
AE
D000818:Animals; D002855:Chromatography, Thin Layer; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D005029:Ethylenediamines; D008995:Monoamine Oxidase