In ancient times, schizophrenia and psychotic disorders were treated in such a way as to combat the various symptoms and perceptual and cognitive disorders.

This would change with the discovery of the first antipsychotics, allowing for the first time patients with these disorders to receive outpatient treatment without requiring hospitalization. One of the first and best known is chlorpromazine .

Chlorpromazine: description and a little history

Chlorpromazine is a substance belonging to the group of antipsychotics or neuroleptics , which have a great effect on the control of psychotic symptoms such as hallucinations, agitation, and delirium.

It is one of the first antipsychotics and belongs to the group of classic or typical neuroleptics. Structurally it is a phenothiazine. Although it is true that although nowadays chlorpromazine is still used in the treatment of psychopathologies such as schizophrenia, the use of other types of antipsychotics is usually preferred due to the risks and side effects that the classics can generate, at the time they were a revolution and served (and still serve in many cases) to greatly improve the quality of life of patients with various mental disorders.

This substance was discovered and synthesized by chance by Paul Charpentier in 1950 while searching for a remedy against malaria. However, some time later Henri Laborit, after observing its tranquilizing effects without necessarily sedating the affected person, began to recommend and establish its use in psychiatry. It would be used for the first time in the treatment of psychotic type psychopathologies in 1951, with a remarkable success that would lead to the discovery to be called the fourth revolution in psychiatry.

Previously, methods used to treat psychotic patients were generally ineffective, risky, and highly aversive and painful to the patient (e.g., inducing insulin-like coma or use of electroshock). The fact that chlorpromazine was effective allowed for a more biologic view of psychotic disorders and would begin to allow for outpatient treatment rather than requiring hospitalization in most cases.

Mechanism of action

As mentioned, chlorpromazine is one of the classic or typical antipsychotics. This type of antipsychotic works by blocking dopamine receptors in the brain, especially the D2 receptor.

The benefit of this blockage is due to the fact that in schizophrenia, positive symptoms such as hallucinations, alterations in thinking and language, distractibility, agitation and restlessness tend to be due to the presence of an excess of dopamine in the mesolimbic pathway. By blocking its emission there is a great improvement in psychotic symptoms of this type.

However, both chlorpromazine and the other classical antipsychotics affect dopamine receptors in a non-specific way, i.e. throughout the brain. Thus, not only is the pathway that has an excess of dopamine affected, but other pathways that had adequate or even low levels are excessively diminished in their levels of this neurotransmitter. It also has an effect on acetylcholine and other neurotransmitters. This causes secondary symptoms of varying severity to appear.

In addition, in schizophrenia other symptoms also appear in which there is a flattening, slowing down or decrease in functions and processes, especially at the cognitive level. The most classic example of these symptoms (called negatives) is alogia or poor thinking. These symptoms are linked to a dopaminergic deficit in the mesocortical pathway , so that the effect of chlorpromazine is not only not positive in these symptoms but could also cause some worsening.

Side effects and risks of chlorpromazine

As with other psychopharmaceuticals, the use of chlorpromazine can have a number of side effects and risks to consider. As mentioned above, by exerting an antagonistic effect on dopamine in all pathways it is possible that problems may arise from this.

One of the main problems derived from the decrease in dopamine, specifically when it occurs in the nigrostriatal pathway, is the appearance of motor disorders such as slowing down, akathisia, dystonia, rigidity and tremors both in themselves and in what is called parkinsonian syndrome. Another common symptom is tardive dyskinesia or the emission of repetitive, involuntary movements of the face and sometimes of the trunk and limbs.

In the tuberous-infundibular pathway, blockage of dopamine can lead to the presence of alterations such as galactorrhea or milk emission from the breasts (regardless of sex), gynecomastia or breast growth (also in both sexes) and alterations in sexual response.

It has also been commented that chlorpromazine and other typical antipsychotics can produce side effects derived from their interaction with acetylcholine . These include mental dullness, constipation, blurred vision or ocular hypertension.

Other frequently reported side effects are a high level of sedation and significant weight gain , and caution should be exercised in cases of eating or metabolic problems. It can also cause problems such as high blood pressure or dizziness, having effects on the cardiovascular system.

Finally, one of the most serious syndromes that can culminate in the death of the patient (although this is very rare) is the neuroleptic malignant syndrome, in which fever, cyanosis, tachycardia and in some cases coma and even death appear. It is in prevention of this syndrome and other problems that the dosage of this type of substance is done with extreme care.

Situations and disorders for which it is indicated

One of the most widespread uses of chlorpromazine is even today (although there is a preference for the use of atypical neuroleptics such as olanzapine because of their greater safety and their effects on negative symptoms) the treatment of schizophrenia and other psychotic disorders .

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However, chlorpromazine has also been shown to be effective in treating manic states. In general it is effective in all situations where positive psychotic symptoms or states of intense motor agitation are present. This includes the presence of delirium and in some withdrawal syndromes. It has been successfully used to reduce Korean symptoms in Huntington’s Korea , and may sometimes be used as a last resort in cases of OCD.

On a more physiological level, we observe that it is sometimes used for the treatment of intestinal problems such as nausea and vomiting (since it is antiemetic), tetanus or porphyria.

Also, given their tranquilizing potential, they have sometimes been used in situations where there are problems with sleep (not surprisingly, antipsychotics were originally called the major tranquilizers). Also in situations with high levels of pain .

Bibliographic references:

  • Gómez, M. (2012). Psychobiology. Manual CEDE de Preparación PIR.12. CEDE: Madrid.
  • Mazana, J.S.; Pereira, J. and Cabrera, R. (2002). Fifty years of chlorpromazine. Revista Española de Sanidad Penitenciaria, vol.4 (3). CP Tenerife II. Medical Services.
  • Salazar, M.; Peralta, C.; Pastor, J. (2006). Manual of Psychopharmacology. Madrid, Editorial Médica Panamericana.