Procaine (Gerovital H3) Therapy: Mechanism of Inhibition of Monoamine Oxidase

Abstract

ABSTRACT: The mechanism by which Gerovital H3 (GH3), a specially stabilized form of procaine hydrochloride, produces a weak inhibition of the enzyme, monoamine oxidase (MAO), was studied by several methods. Purified rat‐brain mitochondrial MAO was used as the enzyme source and the reaction velocities were determined by quantitating the rate of appearance of 4‐hydroxyquinoline from kynuramine. Data on dilutional studies with pre‐incubated enzyme‐inhibitor complexes, as well as other data, strongly indicated that GH3 was a reversible inhibitor of MAO. Analysis of Lineweaver‐Burk and Dixon plots obtained by determining the velocity of oxidation of kynuramine with various concentrations of substrate and inhibitor, showed that GH3 was a fully competitive inhibitor of MAO. The weak, reversible, fully competitive inhibition of MAO produced by GH3 is in marked contrast to the potent, irreversible inhibition of MAO produced by currently available agents. The mechanism by which GH3 inhibits MAO may help to explain the absence of severe adverse reactions with GH3 that are traditionally associated with irreversible MAO inhibitors in the treatment of depressive illness. Because of these characteristics of GH3 as an inhibitor of MAO, assessment of its activity in vivo may not be easily accomplished, despite its pronounced pharmacologic effects.