Two isoenzyme forms:
MAO-A: involved in the metabolism of serotonin, norepinephrine, epinephrine,
catecholamines, tyramine (found in food products such as Chianti wine and aged cheese), and other amines in peripheral tissues… widely distributed!
MAO-B: relatively selective for breakdown of dopamine in CNS, with little activity in
the periphery. MAO-B is found in the striatal tissue of the basal ganglia.
MAO-A inhibitors: (example: pargyline)
The first MAO-inhibitors worked in the periphery, and affected primarily the MAO-A isoform. Thus, if a patient went out and drank half a bottle of Chianti wine (full of tyramine), the tyramine and catecholamines would accumulate. Because the MAO-A was knocked out by the inhibitor, the build up of catecholamines would cause a pressor effect and lead to stroke, MI, and death. Irreversible inhibition of MAO-A results in failure to breakdown various amines, resulting in risk of adverse physiological effects of the amine (e.g., hypertensive crisis when given with tyramine rich foods, OTC cold meds containing phenylephrine, etc; “serotoninergic syndrome” caused by accumulation of excessive 5-HT in CNS).
MAO-B inhibitors:
Relatively selective inhibitor of brain striatal dopamine, including dopamine in non-neuronal structures in the basal ganglia. Useful in enhancing L-dopa therapy in Parkinson’s disease (prevent breakdown of dopa).
Example: selegiline
(Note: selegilene is metabolized in part to amphetamine. Some effects are due to amphetamine-like actions)
Safe rule: do not use MAO inhibitors in patients taking 5-HT enhancing drugs; epinephrine effects will be enhanced. MAO-A inhibitors should neverbe taken concurrently with foods rich in tyramine. MAO-A and MAO-B inhibitors are contraindicated with many drugs and can cause life-threatening drug interactions (e.g., MAO inhibitor + the narcotic meperidine).
