Abstract
Sodium 1,2 - naphthoquinone 4 - sulfonate (NQS), a substance which reacts with alkylhydrazines in a neutral aqueous medium, was found to prevent effectively isocarboxazid-induced MAO inhibition in vitro. Furthermore, when this inhibition was prevented, sufficient isocarboxazid levels to cause complete inhibition were shown to be present. The MAO inhibition induced by benzylhydrazine (BZH), p-dimethylaminobenzylhydrazine, and alkylhydrazide analogs of isocarboxazid (including iproniazid), was also prevented by NQS. But the inhibition caused by 2 nonhydrazine compounds, SKF-385A and A-19l20, was not affected by NQS.
Isocarboxazid, iproniazid, and isopropylhydrazine required a preincubation with the mitochondria of at least 15 minutes to achieve maximum inhibition. The inhibition by BZH was not dependent on the length of the preincubation period. Isocarboxazid was shown to exert equal inhibition when preincubated under oxygen or nitrogen. This was not true for iproniazid where a marked decrease in MAO inhibition was observed when preincubation was conducted under nitrogen.
It is concluded from these experiments that isocarboxazid exerts its MAO inhibition by being hydrolyzed to BZH which is the actual enzyme inhibitor. Furthermore, this conclusion is valid only for isocarboxazid and cannot be extended to explain the mode of action of analogous alkylhydrazides, such as iproniazid, without further investigation.
Footnotes
- Received June 5, 1961.
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