MAO enzymes are found both within the cell and in the synaptic cleft.

They are additionally found in the liver. Therefore, if a pt is on a MAOI and eats foods that have tyramine in them, the tyramine, which is usually metabolized by the MAO enzymes in the liver, can’t be broken down. This leads to potential problems for the pt caused by dangerous food-drug interactions bc of the pressor effects of unmetabolized tyramine on the peripheral vasculature.

Selectivity of MAO enzymes

MAO A – preferred substrates are serotonin, NE, and tyramine

MAO B – preferred substrates are phenylethylamine and dopamine

Selectivity of MAOIs

Most MAOIs inhibit MAO-A and MAO-B non-selectively.

Blockade of MAO-A subtype needed for antidepressant action.

MAO-B is selectively blocked by seligiline (deprenyl) at low doses. At high doses, however, the block is non-specific. (used in treatment of Parkinson’s disease)

MAOIs are essentially all irreversible binders of MAO enzymes. Thus, the duration of action of MAOIs is not related to drug metabolism, but to the regeneration of the enzyme.

Category: Pharmacology Notes