Chlorpromazine: Effects And Uses Of This Psychotropic Drug
In ancient times, schizophrenia and psychotic disorders had a treatment that allowed them to combat the different symptoms and perceptual and cognitive alterations.
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 is a substance belonging to the group of antipsychotics or neuroleptics which have a great effect in the control of psychotic symptoms such as hallucinations, agitation and delirium.
It is one of the first antipsychotics, and is part of the group of classic or typical neuroleptics. Structurally it is a phenothiazine. While it is true that although chlorpromazine is still used today 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 classic ones can generate, at the time they were quite a revolution. and they served (and continue to 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 causing sedation in the affected person, would begin 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 notable success that would lead the discovery to be called the fourth revolution in psychiatry.
Previously, the methods used to treat psychotic patients were generally ineffective, risky and highly aversive and painful for the patient (for example, inducing insulin coma or the use of electroshock). The fact that chlorpromazine was effective allowed a more biological view of psychotic disorders and would begin to allow outpatient treatment to be carried out instead of requiring hospitalization in most cases.
Mechanism of action
As we have mentioned, chlorpromazine is one of the classic or typical antipsychotics. This type of antipsychotics act by blocking dopamine receptors in the brain, especially the D2 receptor.
The fact that this blockade is of benefit is due to the fact that in schizophrenia, positive symptoms such as hallucinations, alterations in thought and language, distractibility, agitation and restlessness tend to be due to the presence of an excess of dopamine in the pathway. mesolimbic. By blocking its emission, there is a great improvement in psychotic symptoms of this type.
However, both chlorpromazine and the rest of the classic antipsychotics affect dopamine receptors nonspecifically, that is, throughout the brain. In this way, not only the pathway that has excess dopamine is affected, but other pathways that had adequate or even low levels see their levels of this neurotransmitter excessively decreased. It also has an effect on acetylcholine and other neurotransmitters. This causes secondary symptoms of varying severity to appear.
In addition, other symptoms also appear in schizophrenia 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 negative) is alogia or poverty of thought. These symptoms They are linked to a dopaminergic deficit in the mesocortical pathway so that the effect of chlorpromazine not only is not positive in these symptoms but could also cause some worsening.
As with other psychotropic drugs, the use of chlorpromazine can have a series of side effects and risks to take into consideration. As we have mentioned previously, by exerting an antagonistic effect on dopamine in all pathways, problems arising from this may arise.
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, akathisia, dystonia, rigidity and tremors both by themselves and in what is called parkinsonian syndrome. Another frequent symptom is tardive dyskinesia or the emission of repetitive and involuntary movements of the face and sometimes of the trunk and extremities.
In the tuberoinfundibular pathway, dopamine blockade can cause the presence of alterations such as galactorrhea or emission of milk 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 may produce side effects derived from their interaction with acetylcholine Among them we find mental dullness, constipation, blurred vision or ocular hypertension.
Other side effects reported with some frequency are a high level of sedation and a notable weight gain, and caution must be taken in cases of dietary 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 and that can lead to death of the patient (although it is very rare) is 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 substances is carried out 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 due to its greater safety and its effects on negative symptoms) the treatment of schizophrenia and other psychotic disorders
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 occur. This includes the presence of delirium and in some withdrawal syndromes. It has been used successfully when reduce choreic symptoms in Huntington’s chorea and sometimes it can be used as a last option in cases of OCD.
At a more physiological level, we observe that it is sometimes used to treat intestinal problems such as nausea and vomiting (since it is antiemetic), tetanus or porphyria.
Likewise, given its tranquilizing potential, it has sometimes also been used in situations in which there are problems with sleep (not in vain, initially antipsychotics were called major tranquilizers). Also in situations that present with high pain
Salazar, M.; Peralta, C.; Pastor, J. (2006). Manual of Psychopharmacology. Madrid, Panamericana Medical Editorial.
