Is promazine an antipsychotic? A Full Pharmacological Review

October 8, 2025 •

3 min read

Promazine was first approved for medical use in the United States in the 1950s. So, is promazine an antipsychotic? Yes, it is classified as a first-generation, or typical, antipsychotic belonging to the phenothiazine class.

Quick Summary

Promazine is classified as a first-generation (typical) antipsychotic. While it has antipsychotic properties, it is considered relatively weak and is noted for its pronounced sedative effects.

Key Points

Classification: Promazine is a first-generation (typical) antipsychotic belonging to the phenothiazine class.
Mechanism: It works primarily by blocking dopamine D2 receptors, but also affects serotonin, muscarinic, histamine, and adrenergic receptors.
Efficacy: It is considered to have weak antipsychotic activity but strong sedative properties.
Primary Use: Historically used for psychomotor agitation, but is no longer recommended or commercially available in the US for humans.
Side Effects: Carries a risk of extrapyramidal symptoms (movement disorders), sedation, anticholinergic effects, and cardiovascular issues.
Modern Relevance: Largely replaced by newer, safer, and more effective atypical antipsychotics.
Toxicity: Promazine is noted to be highly toxic in overdose and can lower the seizure threshold.

Understanding Promazine: Classification and History

Promazine, known by brand names like Sparine, is a medication in the phenothiazine class. Approved in 1956, it's categorized as a first-generation (typical) antipsychotic. Similar to chlorpromazine, promazine is noted for its relatively weak antipsychotic activity and significant sedative effects.

Historically used for psychosis and short-term psychomotor agitation, it's now largely replaced by newer medications with better profiles. The British National Formulary (BNF) lists it as "less suitable for prescribing". It is no longer available in the U.S. for human use but may be used in veterinary medicine.

Mechanism of Action

Promazine, like other typical antipsychotics, primarily blocks dopamine D2 receptors in the brain. It also acts as an antagonist at serotonin (5-HT2A, 5-HT2C), muscarinic (M1-M5), histamine H1, and alpha-1 adrenergic receptors. Blocking H1 receptors causes sedation, while muscarinic receptor blockade leads to anticholinergic effects. Alpha-1 blockade can cause orthostatic hypotension. This broad action profile results in its varied effects and side effects.

Indications and Modern Usage

Promazine's licensed indications narrowed over time due to weaker antipsychotic effects compared to drugs like chlorpromazine. Its main licensed use was for short-term psychomotor agitation, especially in the elderly, although its use for this is now discouraged. Its antihistamine and anticholinergic properties also gave it antiemetic uses. However, its poor side effect profile and the availability of better alternatives have led to its discontinuation for human use in many regions, including the United States.

Side Effects and Safety Concerns

Promazine carries significant risks of side effects typical of first-generation antipsychotics.

Extrapyramidal Symptoms (EPS): Movement disorders like akathisia, dystonia, and parkinsonism can occur. Long-term use can lead to tardive dyskinesia.
Sedation: Significant drowsiness is common due to H1 receptor blockade. Cognitive impairment, especially in the elderly, is also a risk.
Anticholinergic Effects: Dry mouth, constipation, blurred vision, and urinary retention are frequent.
Cardiovascular Effects: Orthostatic hypotension is a risk. QTc prolongation, which can lead to arrhythmias, can also occur.
Neuroleptic Malignant Syndrome (NMS): A rare but serious reaction.
Other Risks: Promazine is highly toxic in overdose and can lower the seizure threshold. Photosensitivity is also a concern.

These risks have led to a preference for newer antipsychotics with better safety profiles.

Comparison: Promazine vs. Modern Antipsychotics

To highlight the shift away from promazine, consider this comparison with Risperidone, an atypical antipsychotic.


Feature	Promazine (Typical/FGA)	Risperidone (Atypical/SGA)
Primary Mechanism	Strong D2 dopamine receptor antagonist.	Potent serotonin (5-HT2A) and dopamine (D2) antagonist.
Efficacy	Relatively weak antipsychotic; more sedating.	Effective against 'positive' and 'negative' symptoms.
Extrapyramidal Symptoms (EPS)	Moderate to high risk.	Lower risk at typical doses.
Metabolic Side Effects	Lower risk.	Higher risk of weight gain and metabolic issues.
Sedation	Pronounced.	Common, but potentially less pronounced.
Primary Use Today	Largely discontinued for human use.	Widely used for schizophrenia, bipolar disorder, etc.

Conclusion

In conclusion, is promazine an antipsychotic? Yes, it is classified as a first-generation, typical antipsychotic in the phenothiazine family. While it blocks dopamine receptors, its weak antipsychotic effects, strong sedation, and considerable risk of side effects like movement disorders and cardiovascular issues have made it largely obsolete in human medicine today. It has been replaced by newer generations of antipsychotics offering better treatment outcomes with fewer side effects.

For further reading on the classification of antipsychotics, you can visit the National Center for Biotechnology Information (NCBI): Adverse Effects and Toxicity of the Atypical Antipsychotics

Frequently Asked Questions

Promazine is in the phenothiazine class of drugs and is classified as a first-generation, or typical, antipsychotic.

No, they are not the same, but they are similar. Promazine is a major metabolite of chlorpromazine and shares a similar chemical structure, but it is considered to have weaker antipsychotic activity.

Promazine was primarily used for the short-term management of psychomotor agitation, restlessness in the elderly, and sometimes for nausea and vomiting. It was also used for psychosis, though it is a relatively weak antipsychotic.

Promazine is generally not prescribed for humans today and is no longer commercially available in the United States. It has been superseded by safer and more effective medications.

The main side effects include significant drowsiness, extrapyramidal symptoms (movement disorders), dry mouth, constipation, and orthostatic hypotension (low blood pressure upon standing).

Promazine is not a first-line treatment because of its relatively weak antipsychotic effect, significant side effect profile, and the availability of newer, more effective, and better-tolerated antipsychotic medications.

A common brand name for promazine was Sparine.