Inhibitor Specificity of Amine Oxidase

In their studies of the oxidation of adrenalin and other amines by amine oxidase preparations, Blaschko, Richter, and Schlossmann (1) found that l-ephedrine, triethylamine, triisoamylamine, and dl-1-hydroxy-2-hydrindeneamine are not only not oxidized, but inhibit the action of the enzyme upon isoamylamine. The conclusion was drawn that this inhibition was of the competitive type, because some data were available which indicated a dependence of degree of inhibition upon the concentration of both enzyme and substrate. Natural l-ephedrine and the related compounds, suprifen and veritol, were later reported by Blaschko (2) to inhibit amine oxidase in its action upon I-sympathol. Some further extension of such studies to include benzedrine, and the finding that this compound and veritol are stronger inhibitors of amine oxidase than are ephedrine isomers in the particular system studied, led Blaschko (3) to conclude there was agreement between the inhibiting effects in vitro on amine oxidase and their awakening properties in animals which are pharmacological effects upon the central nervous system. Previous to this, Gaddum and Kwiatkowski (4) had advanced the theory that ephedrine action in animals was due to its inhibition of adrenalin oxidation by amine oxidase in the body. This was based on demonstration that in the perfused rabbit ear, sympathetic stimulation liberated a substance indistinguishable from adrenalin, and that this substance like adrenalin is increased in certain of its physiological activities by addition of ephedrine. The study by Richter and Tingey (5) of the kinetics of the rate of inactivation of adrenalin by amine oxidase and the degree of inhibition of this oxidation by ephedrine permitted calculations which did not support the view that amine oxidase is specifically concerned in the inactivation of adrenalin in the body. Further evidence obtained by Richter (6) and Richter and Macintosh (7) from their isolation of some of the metabolic products excreted in the urine after administration of adrenalin and other o-diphenolic pressor amines makes it quite certain that adrenalin is not considerably acted on by amine oxidase in passing through the body.