An analysis of the interaction of reversible and irreversible monoamine oxidase inhibitors

Abstract

The interaction of the reversible and irreversible inhibitors of monoamine oxidase (MAO) in the intact rat has been investigated. The results indicate that the extent of antagonism of the irreversible hydrazine inhibitors by harmine or harmaline depends upon two factors: (1) the duration of action of the reversible inhibitor, and (2) the duration of the presence of the irreversible inhibitor in the supernatant fraction (cytoplasmic or interstitial fluid) of the tissue. The duration of harmine was about one-half as long as that of harmaline. Harmine was also less effective as an antagonist of iproniazid. Pheniprazine (PIH) activity disappeared from the supernatant fraction of liver and brain homogenates prepared from rats within 60 to 90 min, whereas iproniazid activity was present for 12–18 hr after administration. It appears that a complete antagonism of PIH by harmine or harmaline results because the reversible inhibitors protect the enzyme from PIH for the duration of its presence. The action of iproniazid is only partly antagonized because it is present in the supernatant for longer periods of time than the reversible inhibitors.