MAO inhibitors

Physiological role of the enzyme and its isoforms

The enzyme monoamine oxidase (MAO) plays a key role in the functioning of the nervous system. Its main physiological function is the oxidative deamination of monoamines, which include norepinephrine, serotonin, and dopamine. The result of this biochemical reaction is the inactivation of neurotransmitters.

In the body, the enzyme is represented by two main isoforms that differ in their substrate specificity:

• MAO-A — primarily inactivates norepinephrine and serotonin. It is the inhibition of this enzyme type that leads to an increase in the content of these neurotransmitters in brain tissues, providing an antidepressant effect.
• MAO-B — primarily inactivates dopamine. Inhibition of MAO-B (for example, by the drug selegiline) increases dopamine levels, which is why it is used for the treatment of parkinsonism, but it does not affect the course of depression.

Non-selective irreversible inhibitors

A classic representative of this group is nialamide. The drug acts as an irreversible and non-selective inhibitor, meaning its targets are both MAO-A and MAO-B enzymes in both the central nervous system and peripheral tissues.

• Pharmacodynamics: The therapeutic effect develops extremely slowly—the latency period ranges from 7 to 14 days of regular administration.
• Recovery: After drug discontinuation, MAO activity recovers very slowly (about two weeks). The reason lies in the irreversible type of inhibition: the body needs time to synthesize brand new enzyme molecules.
• Effects and clinical use: In addition to its antidepressant action, nialamide has a pronounced psychostimulatory effect (capable of causing agitation and eliminating drowsiness). Previously, it was prescribed for depressive states accompanied by lethargy and psychomotor retardation, as well as for angina pectoris (reducing pain sensation).
• Side effects: Due to total enzyme inhibition, the drug causes a wide range of adverse events. Anxiety, insomnia, tremor, and seizures are possible from the central nervous system. From the cardiovascular system, a drop in blood pressure and orthostatic hypotension are observed. Hepatotoxic effects are also characteristic. Because of this, the drug is rarely used today.

Selective reversible MAO-A inhibitors

A modern and safer representative of this group is moclobemide.

• Mechanism of action: The drug selectively and, unlike its predecessors, reversibly inhibits the activity of MAO-A alone. The biochemical result is a temporary suppression of the metabolism of biogenic amines (primarily serotonin and norepinephrine) and an increase in their concentration.
• Advantages: The duration of action of moclobemide is shorter than that of nialamide. While maintaining high efficacy, it has a significantly better safety profile. It lacks pronounced toxic properties, notably hepatotoxicity.

Drug and food interactions

The use of non-selective MAOIs requires strict monitoring due to the risk of severe complications.

1. «Cheese effect» (tyramine syndrome): The development of a severe hypertensive crisis when consuming certain foods while taking nialamide. The triggering agent is tyramine. The list of prohibited foods includes cheese, bananas, soy beans, beer, and yeast extracts. It is important to note that selective moclobemide does not cause this syndrome.
2. Sympathomimetics: Drugs like ephedrine and amphetamine are strictly contraindicated. When MAO is blocked, norepinephrine accumulates in nerve endings, and sympathomimetics provoke its massive release, which manifoldly enhances the pressor (blood pressure-raising) effect.
3. Tricyclic antidepressants: Co-administration with MAOIs is strictly prohibited. A mandatory wash-out period lasting 2–3 weeks is required between courses of these drugs.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Non-selective monoamine reuptake inhibitors (amitriptyline)
• Serotonin-norepinephrine reuptake inhibitors (venlafaxine)
• Selective serotonin reuptake inhibitors (paroxetine)
• Drugs with a receptor mechanism of action: NaSSA (mirtazapine) and SARI (trazodone)
• Selective serotonin reuptake enhancers (tianeptine)

Other topics in the section "Agents Used in Psychiatry and Neurology"

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