MAOIs (monoamine Oxidase Inhibitors): Effects And Types
Although most psychiatrists currently prescribe selective serotonin reuptake inhibitors (SSRIs), norepinephrine reuptake inhibitors (SNRIs) or both neurotransmitters (SNRIs) to treat depressive symptoms, in atypical cases they are still used with some frequency. the oldest type of antidepressant: MAOIs.
In this article we will describe The main effects of 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.
Selective inhibitors of the monoamine oxidase enzyme, commonly known by the acronym “MAOIs”, are the first class of drugs that was used for the treatment of depression The original MAOI, iproniazid, was developed in the 1950s as a tuberculosis medication and attracted attention for its positive effect on mood.
MAOIs exert a agonist effect on monoamine neurotransmitters, the most important of which are dopamine, adrenaline, norepinephrine and serotonin. The same happens with the rest of the antidepressants, among which the tricyclics, the selective serotonin reuptake inhibitors and the fourth generation antidepressants stand out.
The enzyme monoamine oxidase is located in the terminal boutons of the axons of monoaminergic neurons. Its function is to eliminate neurotransmitters of this type to prevent them from accumulating excessively. MAOIs reduce the activity of this enzyme, and consequently increase monoamine levels.
There are two types of MAO enzyme: A and B. While the first deals with the metabolization of serotonin and norepinephrine, 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.
Currently these drugs They are used especially to treat atypical depression, characterized 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, stroke or dementia.
Types of MAOIs
Below we will describe the main characteristics of the three types of drugs in the monoamine oxidase inhibitor class. 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 subtypes of MAO (A and B).
1. Irreversible and non-selective inhibitors
Initially, MAOIs completely destroyed the enzyme monoamine oxidase, preventing its activity until it was synthesized again (which takes place approximately two weeks after the start of pharmacological treatment). This is why they were described as “irreversible.”
Furthermore, the first MAOIs targeted both monoamine oxidase A and B, so that they increased the levels of all monoamines indistinctly. The adjective “non-selective” is derived 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 “cheese effect”, which can cause heart attacks or brain hemorrhages after consuming foods with tyramine 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 risk caused a 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 being marketed we find 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 the enzyme monoamine oxidase) are used to refer to a type of MAOI that does not completely eliminate the enzyme, but rather inhibits its activity for the duration of the drug’s effects. Furthermore, most IRMAs exert their function selectively on MAO A.
The role of the MAO A enzyme is to metabolize norepinephrine and serotonin Since these monoamines are the neurotransmitters most clearly involved in depressive symptoms, selective inhibitors of this subclass of the MAO enzyme are the most useful in the treatment of depression.
The best-known MAOIs A are moclobemide, bifemelane, pirlindole and toloxatone. They are basically used as antidepressants, although moclobemide is also used for the management of social anxiety disorder and panic, 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 norepinephrine and serotonin but with dopamine. This is why, rather than treating depression, MAOIs B are used to slow the progress of Parkinson’s disease However, they are much less common than those that inhibit MAO A.
There are two monoamine oxidase B inhibitors especially used: rasagiline and selegiline. Both are irreversible, meaning they destroy the MAO enzyme rather than temporarily inhibiting its function. Its main area of use is in the early stages of Parkinson’s disease.
