Antipsychotic drugs](antipsychotic drugs) are mainly used to treat the psychotic symptoms of some mental disorders, such as [schizophrenia]/clinical/schizophrenia). However, their indications go much further, and sometimes their chemical characteristics allow for 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 a typical or classic antipsychotic), which can be used to treat schizophrenia (although, as we will see below, it is not its most common use).

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

On the other hand, dopamine is known to be found in high concentrations in people with schizophrenia. That’s why Prochlorperazine is a drug that can be used in this disorder, because it helps lower these dopamine levels.


Chemically, Prochlorperazine is derived from piperazine-infenothiazine (or Piperazine phenothiazines), a type of tricyclic neuroleptic (antipsychotic) drug. Phenothiazines are a group of antipsychotics; specifically, the first ones used in the treatment of psychotic disorders, and the first ones to have positive results in relieving their symptoms.

It can be said that phenothiazines opened the way to 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 purposes.

Piperazine phenothiazines

Piperazine phenothiazines, on the other hand, are a subtype of phenothiazines, from which Prochlorperazine is derived. In other words, Prochlorperazine is a phenothiazine with a piperazine structure. At the chemical and molecular level, piperazine phenothiazines have a piperazine or piperazinil group in 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.

In terms of side effects, piperazine phenothiazines have extrapyramidal (movement-related) disorders. On the positive side, they are fast-acting drugs with 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 leads to a drop 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 discovered first are the classic or typical ones. 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, besides acting on the positive symptoms of psychotic disorders (hallucinations, delusions, disorganized behaviour…), have the advantage that they also act (although to a lesser extent) on the negative symptoms (abulia, emotional flattening, apathy…). Another important difference is that atypicals do not cause extrapyramidal symptoms (symptoms caused by typical antipsychotics).

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

Mechanism of action

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

How does it work? By blocking the dopamine receptors D₂. This blockage affects four main brain pathways, where dopamine plays a key role:

1. Blocking of the mesolimbic pathway

It is the most important blockage in relation to the therapeutic effects of Prochlorperazine (and classical antipsychotics in general), as it involves the reduction of the positive symptoms of schizophrenia. That is, the therapeutic effect of the drug is produced by blocking the mesolimbic pathway of the brain.

2. Blockage of the nigrostriatal pathway

Thus, like all classical antipsychotics, Prochlorperazine also blocks the nigrostriatal pathway, leading to movement disorders (the so-called Extrapyramidal Syndrome [SEP]). These disorders are caused by the decrease in dopamine produced by Prochlorperazine.

3. Mesocortical pathway blockage

The blockage of the third way, the mesocortical one, does not produce any remarkable effect. On the other hand, when dealing with atypical antipsychotics, blocking this pathway improves the negative symptoms of schizophrenia.

4. Blockage of the tube-infundibular pathway

Finally, the blockage produced by Prochlorperazine in the tuber-infundibular pathway, another pathway with a large number of dopamine receptors D₂, produces a series of effects: the most notable is the increase in the concentration of prolactin, which causes gynecomastia (increase in breast size [“breast growth” in both men and women]) and galactorrhea (increase in milk production through the breasts). This is all due to the decrease in dopamine concentration.

Indications and other uses

Prochlorperazine, although indicated for the treatment of schizophrenia, is not as commonly used as an antipsychotic; however, 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 appears that Prochlorperazine also has a “calming” effect and reduces painful symptoms; specifically, it has been found to have a greater effect than hydromorphone (a morphine-derived pain-relieving drug) when applied intravenously, combined with diphenhydramine (a type of antihistamine).

Side effects

Prochlorperazine, like the rest of the classic antipsychotics (with their respective nuances), entails a series of side or adverse effects , such as constipation, headache (migraines), dry mouth, blurred vision, tides, feeling of instability and/or difficulties in maintaining balance, nausea and nasal congestion.

Other symptoms that may be caused are: increased appetite (leading to weight gain), difficulty urinating, dilated or contracted pupils, agitation and/or nervousness, difficulty falling asleep or maintaining sleep (insomnia), drooling, uncontrollable tremors, gynecomastia and galactorrhea (already explained), among others.

These are just some of the symptoms that may occur when taking Prochlorperazine, but there are many others; furthermore, these vary from patient to patient. The dose of Prochlorperazine taken, as well as the frequency with which it is taken, 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.