MAOIs (monoamine oxidase inhibitors): effects and types

This is the first group of psychotropic drugs used to treat depressive disorders.

Although most psychiatrists now prescribe selective serotonin reuptake inhibitors (SSRIs), noradrenaline reuptake inhibitors (SNRIs) or both neurotransmitters (SNRIs) to treat depressive symptoms, the older type of antidepressant, the MAOIs, is still used with some frequency in atypical cases.

In this article we will describe the main effects of the monoamine oxidase enzyme inhibitors and the three types that exist, depending on the subclass of this enzyme that is inhibited by the activity of the drug: irreversible and non-selective MAOIs, MAO A inhibitors and MAO B inhibitors.

What are MAOIs? Effects of these drugs

Selective monoamine oxidase inhibitors, commonly known by the acronym "MAOIs", are the first class of drugs to be used for the treatment of depression. the first class of drugs to be used for the treatment of depression.. The original MAOI, iproniazid, was developed in the 1950s as a drug for tuberculosis and attracted attention for its positive effect on mood.

MAOIs exert an agonist effect on the monoaminergic neurotransmitters, the most important of which areThe most important of which are dopamine, adrenaline, noradrenaline and serotonin. The same is true for the other antidepressants, among which tricyclics, selective serotonin reuptake inhibitors and fourth-generation antidepressants stand out.

The enzyme monoamine oxidase is located in the axon terminal boutons of monoaminergic neurons. Its function is to eliminate neurotransmitters of this type to prevent them from accumulating in excess. MAOIs reduce the activity of this enzyme, and consequently increase the levels of monoamines.

There are two types of MAO enzymeA and B. While the former deals with the metabolization of serotonin and noradrenaline, which are very relevant in depressive symptoms, MAO B is associated with the elimination of dopamine, which is related to a greater extent with other types of disorders, such as Parkinson's disease.

These drugs are currently used primarily to treat are used mainly to treat atypical depressioncharacterized by positive emotional response to pleasant events, weight gain, hypersomnia and sensitivity to social rejection. Some of them are also applied in cases of panic disorder, social phobia, cerebral infarction or dementia.

Types of MAOIs

In the following we will describe the main characteristics of the three types of drugs in the class of monoamine oxidase inhibitors. This division is related to two factors: the intensity of the effects (transient inhibition or total destruction of the MAO enzyme) and the selectivity with respect to the two MAO subtypes (A and B).

1. Irreversible and non-selective inhibitors

Initially, MAOIs completely destroyed the enzyme monoamine oxidaseThey prevent its activity until it is synthesized again (which takes place approximately two weeks after the start of pharmacological treatment). This is why they were described as "irreversible".

In addition, the first MAOIs targeted both monoamine oxidase A and B, so that they increased the levels of all monoamines without distinction. The label "non-selective" derives from this characteristic.

Both MAO A and B enzymes are also responsible for eliminating excess tyramine, the monoamine whose accumulation explains the most characteristic side effects of MAOIs: hypertensive crises or the "cheese effect", which can lead to Heart attacks or cerebral hemorrhages after consuming tyramine-containing foods such as cheese, coffee or chocolate.

Since irreversible, non-selective inhibitors inhibit both enzymes, the increase in tyramine levels associated with their consumption was extreme. Such a risk caused strong interference in the lives of those taking MAOIs of this class and spurred the development of other types of MAOIs with more specific effects.

Among the drugs in this category that are still on the market today are tranylcypromine, isocarboxazid, phenelzine, nialamide and hydracarbazine.. All of them belong to the group of chemical compounds known as hydrazines, with the exception of tranylcypromine.

2. Monoamine oxidase A inhibitors

The abbreviations "RIMA" and "IRMA" (reversible inhibitors of monoamine oxidase enzyme) are used to refer to a type of MAOI that does not completely eliminate the enzyme, but inhibits its activity for the duration of the drug's effects. In addition, most MAOIs exert their function selectively on MAO A.

The role of the MAO A enzyme is to metabolize noradrenaline and serotonin.. Since these monoamines are the neurotransmitters most clearly implicated in depressive symptoms, selective inhibitors of this subclass of the MAO enzyme are the most useful in the treatment of depression.

The best known MAOI A inhibitors are moclobemide, bifemelane, pirlindol and toloxatone. They are basically used as antidepressants, although they are also used in the treatment of depression. moclobemide is also used for the management of social anxiety disorder and panic disorder, and bifemelane is used in cases of stroke and/or senile dementia where depressive-type symptoms are present. and panic disorder, and bifemelane is applied in cases of cerebral infarction and/or senile dementia in which depressive-type symptoms are present.

3. Monoamine oxidase B inhibitors

Unlike monoamine oxidase A, type B is not associated with the inhibition of noradrenaline and serotonin but with that of dopamine. This is why, rather than to treat depression, MAOIs B are used to slow the progression of Parkinson's disease.. However, they are much less common than MAO A inhibitors.

Two monoamine oxidase B inhibitors are particularly widely used: rasagiline and selegiline. Both are irreversible, i.e. they destroy the MAO enzyme rather than temporarily inhibiting its function. Their main area of use is in the early stages of Parkinson's disease.