Microsomal enzymes and potentiation of tyramine pressor response

Therapy with monoamine oxidase (MAO) inhibitors has produced hypertensive crises in patients who have ingested tyramine in food. This effect has been attributed to the inability of inhibited MAO to degrade tyramine, but recent work suggests that inhibition of hepatic microsomal oxidative enzymes may also be involved. In our experiments, SKF-525A was more potent (1000 times) than phenelzine as an inhibitor of microsomal tyramine hydroxylase, but less potent than phenelzine in potentiating the pressor response of tyramine. As SKF-525A was also shown to inhibit MAO (10 times less potent than phenelzine), it is suggested that inhibition of tyramine hydroxylase is not a major factor in potentiating the pressor response. In animals in which the microsomal enzymes were induced with phenobarbital, the pressor response to tyramine was not reduced, as would be expected if microsomal enzymes were regulating tyramine levels. These experiments suggest that tyramine potentiation is probably not a problem in therapy with drugs known to be microsomal enzyme inhibitors if these drugs have no MAO inhibitory activity.