There are many psychopharmaceuticals that have been developed throughout history for the treatment of depression, since the accidental discovery (in fact a drug against tuberculosis was being sought) and the subsequent use in subjects with depression of the first of them.

But although we now have a wide variety of them, the truth is that not all those that were created have seen the light or have continued to be manufactured. Some of them have shown a significant degree of danger, which has led to their no longer being used or to their being withdrawn from sale. This is the case of iproclozid , an antidepressant that was effective at the time but was no longer marketed due to its high hepatotoxicity.

What is iproclozid?

Iproclozid is an antidepressant drug , a psychoactive substance whose properties and effects on the body are very useful in combating the symptoms of depression, such as low mood, anhedonia, fatigue and passivity.

Among antidepressants, iproclozid belongs to the group of monoamine oxidase inhibitors or MAOIs, the first of the types of antidepressants that were synthesized. Specifically, it is a non-selective and irreversible MAOI, which means that it completely destroys the monoamine oxidase enzyme in both its type A and type B.

This group of drugs is highly effective in the treatment of depressive symptoms , but their potency can have dangerous effects on health and they can interact not only with other medications but also with different foods (which implies that their use requires exhaustive control and monitoring). This is why, over time, other safer drugs have been developed that have superseded both the drug that gives its name to this article and the rest of the IMAOS: first were tricyclics and later specific serotonin reuptake inhibitors.

Iproclozid is, as we have said, an effective drug in the treatment of depression, but as an irreversible MAOI its use can generate dangerous side effects and has the potential to cause severe damage to the body, to the point of being associated with possible fulminant liver failure, with the potential for death, and even with several deaths. This is why it was withdrawn from sale and is no longer marketed.

Mechanism of action

The mechanism of action of iproclozid is based on the destruction or blocking of the enzyme monoamine oxidase or MAO, a type of enzyme responsible for eliminating excess monoamine neurotransmitters (among which we find noradrenaline, serotonin and dopamine) that are generated during nerve conduction by means of oxidation processes. There are two types of MAO, A which is responsible for metabolizing serotonin and noradrenaline and B which does the same with dopamine.

The fact that this enzyme is inhibited will prevent such elimination, so that the levels of monoamines in the brain are increased : thus the IMAOS are agonists of the different monoamines. Since noradrenaline and serotonin are essential in depression, this is of great help in combating depressive symptoms.

As we have said, iproclozid is an irreversible and non-selective MAOI. The fact that it is irreversible implies that it is not a blockade of MAO, but that it completely destroys the enzyme and its functioning in the brain (although this is re-synthesized and regenerated after two weeks). And in terms of non-selectivity, we mean that its action is not restricted to one type of MAO, but eliminates all types of this enzyme in the brain.

It also has an effect on tyramine, a substance that is part of many foods and whose excess is also eliminated by MAO. However, as there is no MAO after the action of iproclozid or other MAOIs, it accumulates, and can generate an alteration in blood pressure that sometimes becomes dangerous , or even generate fatal cardiovascular events.

Main indication

Although iproclozid is currently withdrawn from sale due to its high risk, it is a drug whose main indication was the treatment of major depression and other disorders with depressive symptoms.

It also has a sedative and anxiolytic effect that helps to combat states of anxiety, which sometimes made it applied in cases of panic disorder. It has also been observed that it has a certain anticonvulsive and anesthetic effect.

Risks and side effects

Iproclozid is a very powerful drug that affects our brain chemistry in a non-specific and irreversible (temporary) way. Although it has positive effects on disorders such as depression, it should be noted that it is very dangerous. In fact, even other IMAOS that are still in use are only used in atypical depressions and when other drugs have had no effect due to the large number of side effects and risks they have.

Some common, low-risk side effects would be drowsiness or insomnia, dizziness, dry mouth, gastric problems such as nausea and vomiting, constipation or diarrhea, weight gain, decreased libido, or problems with urination.

But beyond that, they can also have serious effects. One of the most relevant risks has to do with their effect on preventing the degradation of tyramine by MAO. This is because the non-degradation of tyramine and its accumulation can lead to sudden and unexpected extreme hypertension, and even to cardiovascular problems, stroke and other similar problems. The risk of serotonin syndrome is also relevant.

Another of the most risky aspects of iproclozid and one of the reasons why its production was paralyzed is because of its strong hepatotoxicity , having been found that in some cases it can cause severe liver problems such as fulminant liver failure and even being linked to some deaths.

Contraindications

Although iproclozid is a drug that is no longer used and sold, it should be borne in mind that if it were to be used, its use would be contraindicated in different types of population (or constant monitoring of its condition would be required).

To begin with, its effect on tyramine means that the consumption of certain foods rich in this substance, such as cheese, meat, beer or sardines among many others, should be avoided, given the risk of increased stress. It would also be totally contraindicated in people with liver problems , as well as in those with cardiac or cardiovascular alterations. Pregnant and lactating women should also avoid it.

It is also contraindicated in people who are being treated with other drugs such as painkillers, other antidepressants, chemotherapy drugs such as doxorubicin or airway relief products such as aminophylline, among many others. This is because the interactions between these drugs can excessively potentiate the effects of one or alter its action on the body. Another sector that should be avoided is obviously those people who are allergic to the drug or any of its components.

Bibliographic references:

  • López-Muñoz, F. and Álamo, C. (2007). History of psychopharmacology. The revolution of psychopharmacology: on the discovery and development of psychopharmaceuticals. Volume II. Madrid. Editorial Médica Panamericana.
  • Pessayre, D., de Saint-Louvent, P., Degott, C., Bernuau, J., Rueff, B., Benhamou, J.P. (1978). Iproclozide fulminant hepatitis. Possible role of enzyme induction. Gastroenterology. 75 (3): 492–496.