Iproniazid: Uses And Side Effects Of This Psychotropic Drug
Depression is a mental health problem that has accompanied human beings throughout history. Already in ancient Greece, melancholy was spoken of as an illness with characteristics similar to what we would consider depression today, with a sad and anhedonic mood. Being also 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.
Iproniazid is a psychotropic drug classified as an antidepressant that also has great historical importance. And it is one of the first antidepressants synthesized, along with substances such as imipramine.
Its discovery was actually accidental, by serendipity , since its synthesis was aimed at finding a drug that was effective against tuberculosis. In trials with patients with tuberculosis, it was observed that it had a mood-elevating effect, something that would eventually be analyzed and applied to the population with depressive disorders (specifically, its use would be approved in 1958).
This medication is part of the group of monoamine oxidase inhibitors or MAOIs, which affect the nervous system by blocking the metabolization of certain neurotransmitters. Iproniazid is in factthe first of the MAOIs marketed and it was, along with other substances derived from it, one of the treatments of choice for patients with depression. Its action occurs in a non-specific and irreversible manner, with its effects continuing 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 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 stand out severe liver problems and promoting high blood pressure to dangerous levels , and the generation of new drugs that do not pose as much risk have meant that MAOIs and especially the first or classic ones are displaced and used only when other drugs fail. In the case of the iproniazid in question, it has currently stopped being marketed given that it is highly dangerous in terms of toxicity, and can only be found in some countries.
Mechanism of action
Iproniazid is, as we have said, a non-selective irreversible monoamine oxidase inhibitor or MAOI. As an MAO, it exerts its effects at the brain level by inhibiting an enzyme, MAO, whose main function is to degrade monoamines through oxidation in order 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, by inhibiting monoamine oxidase, said destruction of monoamines would not occur, so the levels of serotonin, norepinephrine and dopamine will increase in the brain. The action of iproniazid, therefore, would be fundamentally agonist type with respect to monoamines, favoring their action. This will generate an improvement in depressive symptoms by increasing neurotransmitters that are decreased in major depression.
It must be taken into account 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 just that monoamine oxidase is reduced but that it is completely destroyed from our brain until it synthesizes more again (something that can 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.
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 increasing) and anhedonia and feeling of fatigue. Likewise, it has also occasionally been used for the purpose for which it was initially 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 sense, some of the best-known side effects of iproniazid, which in fact it shares with some other MAOIs, are the following.
Firstly and one of the main reasons for its withdrawal is the high level of toxicity that this drug can have for the liver Likewise, another of the possible side effects that has the greatest risk is the appearance of severe hypertensive crises due to its interaction with a large number of foods rich in proteins, which can even contribute to the appearance of strokes or heart problems and vascular with fatal potential.
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 of this means that there are certain types of population that are completely contraindicated for this medication. 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. 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 MAOIs have a high level of interaction with other drugs, and their use with other antidepressants and other drugs is also contraindicated.
