Of all the mental problems, depression is, along with all the anxiety related disorders, one of the most common worldwide. The treatment of this type of problem has been something that has generated an extensive research from multiple scientific disciplines, one of them being psychopharmacology.

Different therapeutic alternatives have been generated and synthesized from this discipline, and there are currently a large number of substances that contribute to the alleviation of both depression and other problems. One of the types of drugs synthesized is extremely interesting since it works in an apparently opposite way to other drugs. These are Serotonin Antagonists and Reuptake Inhibitors or AIRSs .


Antagonists and Serotonin Reuptake Inhibitors: What Are They?

Serotonin Antagonist and Reuptake Inhibitors (SARIs) are a relatively new type of atypical antidepressant characterized by an unusual mechanism of action and seemingly contrary to the way other antidepressants work.

On the one hand, they inhibit the reuptake of serotonin so that its levels at brain level increase, but on the other hand they exert effects contrary to this one in certain receptors of the same one, which in principle reduces the presence and action of this neurotransmitter.

The main and best known representative of this type of drug is trazodone , a drug with therapeutic success both in depression and in other cases of anxious characteristics. Other substances such as nefazodone also have characteristics and mechanisms of action of this type of drug, although given that it also acts to a great extent on other neurotransmitters, they sometimes do not fall within this classification.

However, despite its atypical functioning, this group of drugs has been shown to be useful for the treatment of depressive symptoms as well as other mental conditions and problems.

Mechanism of action

As mentioned above, serotonin antagonists and reuptake inhibitors have a different mechanism of action from other similar drugs.

AIRSs have a dual mechanism of action , generating mainly two types of change in brain chemistry.

On the one hand, they are characterized by generating a blockage in the reuptake of serotonin in presynaptic neurons , which makes this neurotransmitter more present in the synaptic space and can be used by postsynaptic neurons.

On the other hand, the action of this type of drug has an antagonistic effect on the 5HT2A and 5HT2C receptors , preventing serotonin from acting on them. However, in 5HT1A receptors the effect is agonistic, facilitating effects similar to those of serotonin.

It is this last mechanism of action that makes the way the AIRS act somewhat different and peculiar if we compare it with other more well-known types of antidepressant, possessing anxiolytic and hypnotic properties.

Therapeutic indications of AIRS

Serotonin antagonists and reuptake inhibitors are substances classified as antidepressants, so their main indication is the treatment of major depression .

These drugs also have anxiolytic action, making them effective for the treatment of various anxiety related conditions. Thus, they have been used (specifically with regard to trazodone) in problems such as generalized anxiety, psychogenic erectile dysfunction, bulimia nervosa, OCD, or withdrawal syndromes.

They are also used in sleep problems, such as insomnia, because they have a hypnotic and sedative effect . This effect has also been used in some cases of bipolar disorder or psychotic disorders such as schizophrenia.

Side effects

Like all psychopharmaceuticals, AIRSs can have a variety of side effects. Nausea and vomiting (especially in the first few weeks), sedation and fatigue, tiredness, low blood pressure, edema or blurred vision are common.

There may also be a risk that suicidal ideation, which is common to many antidepressants, may appear more easily in the first few weeks. Priapism and arrhythmias can also appear and have consequences in people with previous cardiovascular problems.

It should be noted that the main representative of these drugs is excreted in breast milk, which is contraindicated in pregnant and lactating women. Also in people with heart problems and previous infarctions and liver or kidney problems. Special caution should be taken in cases of bipolarity or psychotic disorder, since it may favour a turn to manic symptoms or the appearance of positive symptoms such as hallucinations and agitation.

Bibliographic references:

  • Alcántara-López, M.G.; Gutiérrez-García, A.G.; Hernández-Lozano, M. & Contreras, C.M. (2009). Trazodone, an atypical antidepressant with anxiolytic and sedative properties. Arch. Neurocien (Mex), 14 (4): 249-257.
  • Pérez, R. (2017). Pharmacological treatment of depression: current and future directions. Rev. Fac. Med. (Mexico), 60 (5). Mexico City.