Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors are among the oldest antidepressant agents, acting by blocking the enzyme monoamine oxidase, which normally degrades serotonin, norepinephrine, and dopamine. By inhibiting this breakdown they raise the availability of all three monoamines. Their interaction with dietary tyramine and with other serotonergic drugs gives the class a distinctive safety profile that shaped how it is positioned among antidepressants.

Definition

Monoamine oxidase inhibitors are antidepressants that inhibit monoamine oxidase, the enzyme responsible for the oxidative deamination of monoamine neurotransmitters, thereby increasing the availability of serotonin, norepinephrine, and dopamine.

Scope

This entry covers the enzymatic mechanism that defines the MAOI class, the distinction between its enzyme subtypes, and the basis for the dietary and drug interactions that characterise it. It treats the material as pharmacology reference rather than prescribing guidance.

Core questions

• How does enzyme inhibition differ from reuptake inhibition as an antidepressant mechanism?
• What distinguishes monoamine oxidase A from monoamine oxidase B?
• Why does the class carry distinctive dietary and drug-interaction considerations?

Key concepts

• Monoamine oxidase enzyme (MAO-A and MAO-B)
• Inhibition of monoamine breakdown
• Reversible versus irreversible inhibition
• Tyramine interaction
• Risk of serotonin excess with serotonergic drugs

Mechanisms

MAOIs inhibit monoamine oxidase, the mitochondrial enzyme that catabolises monoamine neurotransmitters. Two isoforms exist: MAO-A preferentially metabolises serotonin and norepinephrine, while MAO-B preferentially metabolises other amines, and inhibitors differ in their selectivity and in whether their binding is reversible or irreversible. Inhibition of MAO-A also reduces metabolism of dietary tyramine, which can lead to a pressor response, and combining these agents with other serotonergic drugs can produce excess serotonergic activity; these interactions account for the class's distinctive precautions.

Clinical relevance

MAOIs are an important reference class because they illustrate an antidepressant mechanism based on enzyme inhibition rather than transporter blockade, and because their interaction profile explains why they are positioned differently from newer agents. This description is for reference only and is not dosing, selection, or individualised treatment advice.

Evidence & guidelines

MAOIs are recognised as effective antidepressants and appear in comparative analyses of the antidepressant armamentarium, though their interaction profile has contributed to their being used less commonly than newer classes.

History

The antidepressant effect of the monoamine oxidase inhibitor iproniazid was recognised in the 1950s, making MAOIs one of the first antidepressant classes and a key contributor to the monoamine hypothesis of depression. The later distinction of MAO subtypes and the development of reversible and selective inhibitors refined understanding of the class.

Key figures

• Joseph Schildkraut

Seminal works

• schildkraut-1965
• belmaker-2008

Frequently asked questions

How do MAOIs raise monoamine levels?

They inhibit monoamine oxidase, the enzyme that breaks down serotonin, norepinephrine, and dopamine, so blocking the enzyme increases the availability of these neurotransmitters.

What is the difference between MAO-A and MAO-B?

MAO-A preferentially metabolises serotonin and norepinephrine, while MAO-B preferentially metabolises other amines; inhibitors vary in which isoform they target and in whether their action is reversible.