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, 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, MAOA inhibitors and MAOB inhibitors.
What are MAOIs? Effects of these drugs
Selective monoamine oxidase inhibitors, commonly known by the acronym “MAOIs”, are the first class of drugs that was used to treat 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 monoaminergic neurotransmitters , the most important of which are dopamine, adrenaline, noradrenaline and serotonin. The same is true of the other antidepressants, the most important of which are tricyclics, selective serotonin reuptake inhibitors and fourth-generation antidepressants.
The enzyme monoamine oxidase is located in the terminal buttons of the axons of monoaminergic neurons. Its function is to eliminate such neurotransmitters 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 enzyme : A and B . While the first deals with the metabolism of serotonin and noradrenaline, which are very relevant in depressive symptoms, MAO B is associated with the elimination of dopamine, which is more related to other types of disorders, such as Parkinson’s disease.
Currently these drugs are used mainly 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 describe the main characteristics of the three types of drugs in the MAOI 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 MAO subtypes (A and B).
1. Irreversible and non-selective inhibitors
Initially the MAOI completely destroyed the enzyme monoamine oxidase , preventing its activity until it was synthesized again (which takes place approximately two weeks after the start of the drug treatment). This is why they were classified as “irreversible”.
In addition, the early MAOIs targeted both monoamine oxidase A and B, so they increased the levels of all monoamines indiscriminately. The adjective “non-selective” is derived from this characteristic.
Both the 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 haemorrhages after consuming foods with tyramine such as cheese, coffee or chocolate.
Since irreversible and 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.
Drugs in this category that are still on the market include tranylcypromine, isocarboxazid, phenelzine, nialamide and hydrazrazine . 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 monoamine oxidase inhibitors) are used to refer to a type of MAOI that does not completely eliminate the enzyme, but inhibits its activity while the drug’s effects last. In addition, most MAOIs work selectively on MAOA.
The role of the enzyme MAO A is to metabolize noradrenaline and serotonin . Because these monoamines are the neurotransmitters most clearly involved in depressive symptoms, selective inhibitors of this subclass of MAO enzyme are the most useful in the treatment of depression.
The best known MAOA are moclobemide, bifemelane, pyrrolindol and toloxatone. They are basically used as antidepressants, although l a moclobemide is also used for the management of social anxiety disorder and panic disorder, and bifemelane is applied in cases of cerebral infarction and/or senile dementia where depressive-type symptoms are present.
3. Monoamine oxidase B inhibitors
Unlike monoamine oxidase A, type B is not associated with noradrenaline and serotonin inhibition but with dopamine inhibition. This is why, rather than treating depression, MAOI B is used to slow the progression of Parkinson’s disease . However, they are much less common than those that inhibit MAO A.
There are two specially used MAO-B inhibitors: rasagiline and selegiline. Both are irreversible, that is, they destroy the MAO enzyme instead of temporarily inhibiting its function. Their main area of use is in the early stages of Parkinson’s disease.