Ribbon diagram of a monomer of human MAO-A, with FAD and clorgiline bound, oriented as if attached to the outer membrane of a mitochondrion. From .<unk> s act by inhibiting the activity of monoamine<unk> , thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine<unk> , MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and norepinephrine. MAO-B preferentially deaminates phenethylamine and certain other trace amines; in contrast, MAO-A preferentially deaminates other trace amines, like tyramine, whereas dopamine is equally deaminated by both types. Reversibility The early<unk> s covalently bound to the monoamine<unk>  enzymes, thus inhibiting them irreversibly; the bound enzyme could not function and thus enzyme activity was blocked until the cell made new enzymes. The enzymes turn over approximately every two weeks. A few newer<unk> s, a notable one being moclobemide, are reversible, meaning that they are able to detach from the enzyme to facilitate usual catabolism of the substrate. The level of inhibition in this way is governed by the concentrations of the substrate and the<unk> . Harmaline found in Peganum harmala, Banisteriopsis caapi, and Passiflora incarnata is a reversible inhibitor of monoamine<unk>  A (RIMA). Selectivity In addition to reversibility,<unk> s differ by their selectivity of the MAO enzyme subtype. Some<unk> s inhibit both MAO-A and MAO-B equally, other<unk> s have been developed to target one over the other. MAO-A inhibition reduces the breakdown of primarily serotonin, norepinephrine, and dopamine; selective inhibition of MAO-A allows for tyramine to be metabolised via MAO-B. Agents that act on serotonin if taken with another serotonin-enhancing agent may result in a potentially fatal interaction called serotonin syndrome or with irreversible and unselective inhibitors (such as older<unk> s), of MAO a hypertensive crisis as a result of tyramine food interactions is particularly problematic with older<unk> s. Tyramine is broken down by MAO-A and MAO-B, therefore inhibiting this action may result in its excessive build-up, so diet must be monitored for tyramine intake. MAO-B inhibition reduces the breakdown mainly of dopamine and phenethylamine so there are no dietary restrictions associated with this. MAO-B would also metabolize tyramine, as the only differences between dopamine, phenethylamine, and tyramine are two phenylhydroxyl groups on carbons 3 and 4. The 4-OH would not be a steric hindrance to MAO-B on tyramine. Selegiline is selective for MAO-B at low doses, but non-selective at higher doses.
Monoamine oxidase inhibitor
Acetylcholinesterase inhibitor
Dopamine antagonist
Enkephalinase inhibitor
Monoamine reuptake inhibitor
Norepinephrine reuptake inhibitor
Glycine reuptake inhibitor
Opioid antagonist