Inhibition of monoamine oxidase activity by phenylpropanolamine, an anorectic agent.

Phenylpropanolamine (PPA) can cause hypertensive crisis in the event of abusive overdosage. It would be interesting to know if this is related to inhibition of monoamine oxidase (MAO) activity. PPA was found to inhibit both human brain and rat liver mitochondrial MAO activities in vitro, i.e. Ki's were 150 microM and 800 microM with respect to serotonin (Type A substrate) and beta-phenylethylamine (Type B substrate). The inhibition is competitive and reversible. PPA can also inhibit MAO-A activity in vivo at relatively high dose (50 mg/kg, i.p.), which was determined from an observation that PPA can protect MAO from the irreversible MAO inhibitor clorgyline. p-Tyramine levels were found to be increased in the urine after i.p. administration of PPA. Chronic administration of PPA does not induce any accumulative inhibitory effect on rat brain and liver MAO activities.