Prochlorperazine (Antipsychotic): Uses, Indications, and Side Effects

[Antipsychotic drugs](antipsychotic drugs) are mainly used to treat psychotic symptoms typical of some mental disorders, such as [schizophrenia]/clinical/schizophrenia). However, their indications go much further, and sometimes their chemical characteristics allow the relief of other types of symptoms.

This is what happens with Prochlorperazine, a classic antipsychotic drug, which also has antiemetic effects and antivertigo activity.. It is a type of piperazine phenothiazine, a group of antipsychotics. In this article we will know its characteristics, mechanism of action, uses, indications and side effects.

Prochlorperazine: characteristics

Prochlorperazine is a first-generation antipsychotic drug (also called typical antipsychotic or classic), which can be used to treat schizophrenia (although, as we will see later, its use is not more frequent).

Its mechanism of action is to antagonize the dopamine D₂ receptor., which leads to a decrease in the concentration of this substance. The commercial name of Prochlorperazine is: Stemetil.

On the other hand, it is known that dopamine is found in elevated concentrations in people with schizophrenia. That is why Prochlorperazine is a medication that can be used in this disorder, because it helps to decrease said concentrations of dopamine.

phenothiazines

At a chemical level, Prochlorperazine derives from piperazinephenothiazine (or Piperazine Phenothiazines), a type of tricyclic neuroleptics (antipsychotics). The phenothiazines are a group of antipsychotics; specifically, the first ones used in the treatment of psychotic disorders, and the first ones that obtained positive results to alleviate their symptoms.

It can be said that phenothiazines ushered in the era of psychopharmacology. They are currently used to relieve psychotic symptoms, but also to prevent nausea and vomiting. (they are antiemetics), reduce hypertension (antihypertensives) and relieve allergic symptoms (antihistamines). In addition, they are used for other therapeutic uses.

Piperazine phenothiazines

Piperazine phenothiazines, for their part, are a subtype of phenothiazines, from which Prochlorperazine derives. In other words, Prochlorperazine is a phenothiazine with a piperazine structure. At the chemical and molecular level, piperazine phenothiazines have a piperazine or piperazinyl group on their side chain.

This subtype of phenothiazines, the piperazine phenothiazines, is the most potent of the phenothiazines. They have characteristics that allow them to be used for long-term treatment (chronic treatment) in patients with schizophrenia.

At the level of side effects, piperazine phenothiazines present extrapyramidal disorders (related to movement). On the positive side, they are fast-acting drugs that cause little sedative action.

On the other hand, another advantage of Prochlorperazine, and piperazine phenothiazines in general, is that they do not cause orthostatic hypotension (or if they do, it is to a very small degree). Orthostatic hypotension entails a decrease in blood pressure; Specifically, it is the body's inability to regulate blood pressure quickly.

Classic or typical antipsychotics

Antipsychotics, also called neuroleptics, can be of two types: classic (first generation or typical) and atypical (second generation). Those that were discovered first are the classics or typical. As we have seen, Prochlorperazine belongs to the first group.

The most important difference between these two groups of antipsychotics is that the atypical ones, in addition to acting on the positive symptoms of psychotic disorders (hallucinations, delusions, disorganized behavior...), have the advantage that they also act (although to a lesser extent) on negative symptoms (apathy, flattening affective, apathy…). Another important difference is that atypicals do not cause extrapyramidal symptoms (symptoms that typical antipsychotics do).

However, in terms of efficacy, both types of antipsychotics are equally effective. The important thing is to find the antipsychotic that best suits the characteristics of the patient. and its pathology.

Mechanism of action

Thus, Prochlorperazine in particular is a typical antipsychotic. Therefore, it presents the characteristics of this type of antipsychotics.

How does it act? Blocking dopamine D₂ receptors. This blockade affects four main brain pathways, where dopamine plays an essential role:

1. Mesolimbic pathway block

It is the most important block in relation to the therapeutic effects of Prochlorperazine (and the classic antipsychotics in general), since it implies the reduction of the positive symptoms of the schizophrenia. That is, the therapeutic effect of the drug occurs thanks to the blockade of the mesolimbic pathway of the brain.

2. Blockage of the nigrostriatal pathway

Thus, like all classic antipsychotics, Prochlorperazine also blocks the nigrostriatal pathway, which leads to movement disorders (the so-called Extrapyramidal Syndrome [EPS]). These alterations appear due to the decrease in dopamine produced by Prochlorperazine.

3. Mesocortical pathway block

The blockade of the third way, the mesocortical, does not produce any notable effect. In contrast, when it comes to atypical antipsychotics, blocking this pathway improves the negative symptoms of schizophrenia.

4. Blockage of the tuberoinfundibular pathway

Finally, the blockade produced by Prochlorperazine in the tuberoinfundibular pathway, another pathway with a large number of dopamine D₂ receptors, produces a series of effects: the most notable is the increase in the concentration of prolactin, which causes gynecomastia (increased breast size ["breasts grow" in both men and women]) and galactorrhea (increased milk production through the breasts). This is all due to the decreased concentration of dopamine.

Indications and other uses

Prochlorperazine, although indicated for the treatment of schizophrenia, is not used as frequently as an antipsychotic; however, yes it is used especially as an antiemetic drug to reduce and relieve nausea and vomiting (at lower doses than as an antipsychotic). On the other hand, Prochlorperazine is also frequently used to treat dizziness and so-called "severe labyrinthine disorders".

In addition, Prochlorperazine is used to treat headaches and acute migraines (although this is not an official or authorized indication; this concept is called “off label”).

Finally, it seems that Prochlorperazine also has a "soothing" effect and reduces painful symptoms; specifically, its effect has been seen to be greater than that of hydromorphone (an analgesic drug derived from morphine) when given intravenously, combined with diphenhydramine (a type of antihistamine).

Side effects

Prochlorperazine, like the rest of the classic antipsychotics (with their respective nuances), carries a series of side or adverse effects, such as constipation, headache (migraines), dry mouth, blurred vision, dizziness, feeling unsteady and/or difficult to keep your balance, nausea, and nasal congestion.

Other symptoms that it can cause are: increased appetite (which leads to weight gain), difficulties urinating, dilation or contraction of the pupils, agitation and/or nervousness, difficulties falling asleep or staying asleep (insomnia), drooling, uncontrollable tremors, gynecomastia and galactorrhea (already explained), among others.

These are just some of the symptoms that can appear when taking Prochlorperazine, but there are many others; in addition, these vary from one patient to another. The dose of Prochlorperazine that is taken, as well as its frequency of taking, can vary the manifestations of side effects.

Bibliographic references:

• Stahl, S.M. (2002). Essential Psychopharmacology. Neuroscientific bases and clinical applications. Barcelona: Ariel.

• Malgor, L. and Valsecia, M. (2008). Psychopharmacology. Chapter 3: Neuroleptics, antipsychotics or major tranquilizers: 24-36. medical pharmacology.