Categories: Drugs

Contraindications and side effects of Iproniazid

Discover the contraindications and side effects of Iproniazid.

It was one of the first antidepressant drugs, and it was discovered by chance.

This was the first representative of the drugs belonging to the group of MAOIs.

Depression is a mental health problem that has accompanied human beings throughout history.

Already in ancient Greece melancholy was spoken of as a disease with characteristics similar to what we would consider today depression, with a sad and anhedonic state of mind.

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Also being currently one of the most prevalent disorders worldwide, the search for an effective treatment has generated great interest over time and has become an increasingly pressing need.

There are various methods used to treat this condition, including psychopharmacology. One of the first drugs to be found and synthesized was iproniazid, which we will talk about throughout this article.

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Iproniazid: the first MAOI

Iproniazid is a psychotropic drug classified as an antidepressant that also has great historical importance.

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And it is one of the first synthesized antidepressants, along with substances such as imipramine.

His discovery was accidental, by serendipity, since his synthesis was aimed at finding a drug that would be effective against tuberculosis.

In trials with tuberculosis patients, it was observed that it had a mood-elevating effect, something that would be analyzed over time and applied to the population with depressive disorders (specifically, its use would be approved in 1958).

This medicine is part of the group of monoamine oxidase inhibitors or MAOIs, which affect the nervous system by blocking the metabolism of certain neurotransmitters.

Iproniazid is the first of the MAOIs marketed and was, together with other substances derived from it, one of the treatments of choice for patients with depression.

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Its action occurs in a non-specific and irreversible way, its effects being continuous for at least fifteen days.

At the level of effects, its application generates an increase in mood and activation, being effective in the treatment of depressive symptoms and reducing the inactivity and passivity of those who use it.

However, the observation of the existence of strong side effects that put the health of those who consumed it at risk, among which are severe liver problems and the promotion of high blood pressure to dangerous levels, and the generation of new drugs that do not pose as much risk They have caused MAOIs and especially the first or classic ones to be displaced and used only when other drugs fail.

In the case of iproniazid in question, it is currently no longer marketed since it is highly dangerous in terms of toxicity, and can only be found in some countries.

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Mechanism of action

Iproniazid is, as we have said, an irreversible non-selective monoamine oxidase or MAOI inhibitor.

As MAOI, it exerts its effects at the brain level by inhibiting an enzyme, MAO, whose main function is to degrade monoamines through oxidation to eliminate excess neurotransmitters generated by monoaminergic neurons (which are those that generate dopamine, norepinephrine, and serotonin) in the synaptic space as well as tyramine.

Thus, inhibiting monoamine oxidase would not produce said destruction of monoamines, with which the levels of serotonin, norepinephrine, and dopamine will increase in the brain.

The action of iproniazid, then, would be fundamentally agonist concerning monoamines, favoring their action.

This will generate an improvement in depressive symptoms by increasing neurotransmitters that are decreased in major depression.

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It should be borne in mind that there are two types of monoamine oxidase: MAO A and MAO B.

The first is linked and is responsible for metabolizing and destroying excess norepinephrine, serotonin, and tyramine, the first two being the substances most linked to depression.

MAO B does the same with dopamine, also influencing tyramine like the previous one.

The fact that it is considered irreversible and non-selective implies that iproniazid acts on all types of MAO, in such a way that it is not only that monoamine oxidase is reduced but that it is destroyed from our brain until it synthesizes more (something which may take around fifteen days).

But the truth is that the enzyme in question is useful to the brain, and the increase in neurotransmitters it generates (especially in the case of tyramine and norepinephrine) can have dangerous effects on health.

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Main indications

Iproniazid is a drug that is not currently marketed due to the high level of risk it poses in terms of liver toxicity and the existence of much safer drugs with fewer side effects.

However, the main indication for this drug was in cases of major depression, being effective in the treatment of symptoms at the level of mood (which contributed to increase) and anhedonia and a feeling of fatigue.

Likewise, it has also occasionally been used for the purpose for which it was originally intended: the treatment of tuberculosis.

Side effects, contraindications, and risks

Iproniazid is a drug that is very useful in the treatment of depressive symptoms, but, as we have mentioned, it has been withdrawn from the market due to its high level of risk and the side effects it has.

In this regard, some of the best-known side effects of iproniazid, which it shares with some other MAOIs, are as follows.

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In the first place and one of the main reasons for its withdrawal is the high level of toxicity that this drug can have on the liver.

Likewise, another of the possible side effects that have the highest risk is the appearance of severe hypertensive crises due to its interaction with a large number of foods rich in protein, which can even contribute to the appearance of strokes or heart problems and life-threatening vascular diseases.

It can also cause kidney problems. Other less serious symptoms are the appearance of insomnia, weight gain and difficulties or inability to reach orgasm, delayed ejaculation, or decreased libido.

All this means that certain types of populations have this medication contraindicated.

In this sense, all those people who suffer from some type of pathology or liver damage stand out, as well as those with heart disease or kidney problems.

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People who require a high protein diet also have it highly contraindicated. People with diabetes and celiac disease should not take this drug either.

Iproniazid and other MAOS have a high level of interaction with other drugs, and their use with other antidepressants and other drugs is also contraindicated.

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