Phenylhydrazine (PhNNH2) was found to irreversibly inhibit both human brain type A and type B monoamine oxidase (MAO) in vitro. PhNNH2 was a more effective inhibitor of the B form of the oxidase in that 50 per cent inhibition of phenylethylamine (PEA) deamination occurred at approximately 4 μM, whereas the equivalent inhibition of 5-hydroxytryptamine (5-HT) deamination required almost 200 μM of the inhibitor. Similarly, inhibition of PEA deamination occurred at a faster rate than that of 5-HT metabolism. Evidence is presented that suggests that PhNNH2 inhibits both forms of MAO by two distinct mechanisms, a temperature-sensitive and a temperature-insensitive process. The temperature-insensitive component proceeded extremely rapidly, compared to the temperature-dependent component. For example, at 4° inhibition of PEA deamination by PhNNH2 attained its maximum within a 30-sec preincubation period. Both inhibition processes were diminished when PhNNH2 was preincubated in a nitrogen atmosphere compared to that in air. Fifty per cent inhibition of PEA and 5-HT deamination by the PhNNH2 temperature-insensitive component occurred at 20 μM and 1 mM respectively. The presence of two distinct inhibition processes is consistent with prior studies that have demonstrated that more than 1 mole of PhNNH2 is bound per mole of MAO.
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