Prochlorperazine maleate
[CAS# 84-02-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Isoquinoline compound
• Name: Prochlorperazine maleate
• Synonyms: Prochlorperazine maleate; Stemetil; Stemetil dimaleate; Vertigon; 2-Chloro-10-[3-(4-methyl-1-piperazinyl)propyl]phenothiazine dimaleate; Buccastem
• Molecular Formula: C₂₀H₂₄ClN₃S^.2(C₄H₄O₄)
• Molecular Weight: 606.09
• CAS Registry Number: 84-02-6
• EC Number: 201-511-3
• SMILES: CN1CCN(CC1)CCCN2C3=C(SC4=CC=CC=C24)C=CC(=C3)Cl.C(=C\C(=O)O)\C(=O)O.C(=C\C(=O)O)\C(=O)O

Properties

• Melting point: 228 �ºC (Expl.)
• Solubility: Soluble 25 mM (DMSO) (Expl.)

^* FR 1167627 1958.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H312-H332
• Precautionary Statements: P261-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P321-P330-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Serious eye damage	Eye Dam.	1	H318
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Skin sensitization	Skin Sens.	1	H317
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400

Discovory and Applicatios

Prochlorperazine maleate is a salt form of prochlorperazine, a synthetic derivative of the phenothiazine class of compounds that functions primarily as an antiemetic and antipsychotic agent. Its molecular formula is C₂₀H₂₄ClN₃S·C₄H₄O₄, indicating the combination of the active base with maleic acid. The compound appears as a white or slightly yellowish crystalline powder and is soluble in water and alcohol.

Prochlorperazine was first introduced in the 1950s as part of a wave of phenothiazine derivatives developed following the clinical success of chlorpromazine. The addition of a piperazine ring at position 10 of the phenothiazine structure increased its potency and selectivity, particularly for dopamine D₂ receptors in the central nervous system. The maleate salt form was chosen to enhance the compound’s stability and aqueous solubility for pharmaceutical formulations.

The primary mechanism of action of prochlorperazine involves antagonism of dopamine D₂ receptors in the chemoreceptor trigger zone (CTZ) of the medulla oblongata, which suppresses nausea and vomiting. This effect has made it widely used for the control of severe nausea, vomiting due to chemotherapy, radiation therapy, postoperative states, and certain gastrointestinal conditions. In psychiatry, prochlorperazine is also employed in the management of schizophrenia and other psychotic disorders, where its dopamine-blocking properties contribute to reducing delusions, hallucinations, and thought disturbances.

Prochlorperazine maleate is typically administered orally, rectally, or by intramuscular injection. Oral tablets are the most common form, often dosed in strengths of 5 or 10 milligrams. Suppositories and injectable solutions are used when oral administration is not feasible, especially in acute care settings. The dosage and route depend on the severity of the condition being treated, the patient's age, and response to therapy.

As with other phenothiazines, prochlorperazine maleate can cause a range of side effects. The most common include drowsiness, dizziness, dry mouth, blurred vision, and constipation. At higher doses or with prolonged use, extrapyramidal symptoms such as dystonia, akathisia, parkinsonism, and tardive dyskinesia may occur. Rare but serious adverse effects include neuroleptic malignant syndrome, hypotension, and agranulocytosis. Due to these risks, monitoring is recommended during long-term therapy, especially in elderly patients or those with a history of neurologic conditions.

Pharmacokinetically, prochlorperazine is well absorbed when administered orally and undergoes extensive first-pass metabolism in the liver. It is highly protein-bound in plasma and has a relatively long half-life, allowing for sustained therapeutic effects. The compound is metabolized primarily through hepatic oxidative pathways, and its metabolites are excreted in the urine and bile.

From an analytical standpoint, prochlorperazine maleate can be identified and quantified using various techniques, including ultraviolet-visible (UV-Vis) spectroscopy, high-performance liquid chromatography (HPLC), and mass spectrometry. Infrared (IR) spectroscopy is used to confirm the presence of functional groups such as aromatic rings, amines, and maleate-associated carboxylic acids. Thin-layer chromatography (TLC) is also commonly employed in pharmaceutical quality control.

Prochlorperazine maleate is listed in several pharmacopeias, including the United States Pharmacopeia (USP) and European Pharmacopoeia (Ph. Eur.), which provide specifications for its purity, identification, and assay methods. Its stability is generally good under standard storage conditions, though formulations should be protected from light and moisture.

In summary, prochlorperazine maleate is a clinically important compound used for the treatment of nausea, vomiting, and psychotic disorders. Its development marked a significant advance in the therapeutic application of phenothiazines, particularly in antiemetic care. Despite the availability of newer agents, prochlorperazine remains a valuable option in clinical medicine due to its established efficacy, broad utility, and diverse routes of administration.

References

2023. A case of carcinoid syndrome probably exacerbated by hemodialysis in which prochlorperazine maleate was effective. CEN Case Reports, 12(4).
DOI: 10.1007/s13730-023-00814-6

2021. A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department. Headache: The Journal of Head and Face Pain, 61(4).
DOI: 10.1111/head.14091

2020. Antiviral activity of chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine towards RNA-viruses. A review. European Journal of Pharmacology, 886.
DOI: 10.1016/j.ejphar.2020.173553