SOME EFFECTS OF MONOAMINE OXIDASE INHIBITORS ON THE METABOLISM OF γ‐AMINOBUTYRIC ACID IN RAT BRAIN

Abstract— (1) The inhibitor of γ‐aminobutyrate transaminase (GABA‐T), amino‐oxyacetic acid (AOAA), drastically reduced the activity of GABA‐T to 30 per cent of the control value, with a corresponding increase of brain GABA, but had no effect on the activity of glutamate decarboxylase (GAD). (2) The monoamine oxidase (MAO) inhibitors phenelzine, phenylpropylhydrazine and phenylvalerylhydrazine, lowered GABA‐T activity to 58, 49 and 48 per cent, respectively; this was associated with a marked elevation of brain GABA. (3) The action of phenelzine and phenylpropylhydrazine in vivo and in vitro could be abolished by pre‐treatment of the tissue with the structurally related MAO inhibitors phenylisopropylhydrazine and trans‐2‐phenylcyclopropylamine. These had no action on the GABA system in vivo, either on the GABA content or on the GABA‐T activity. These latter drugs, however, were unable to influence the effects of AOAA either on GABA or on GABA‐T. (4) The possible mechanism of action on GABA and the enzyme activities of the GABA system is discussed.