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Prochlorperazine
Prochlorperazine is used as a first-generation antipsychotic1 and antiemetic2. It treats severe nausea and vomiting,3 migraines,1 and schizophrenia,3 and is a less preferred treatment for anxiety. Early literature suggested chlorpromazine-to-prochlorperazine antipsychotic dose-equivalence ratios ranging from 2:1 to 5:1.4 Common side effects include sleepiness, blurred vision, low blood pressure, and dizziness.2 Serious adverse effects can include movement disorders such as tardive dyskinesia and neuroleptic malignant syndrome.1
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Duration
Subjective Effects
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Effects vary widely by individual, dose, and context.
Physical
The physical effects of prochlorperazine can be broken down into several components which progressively intensify proportional to dosage.
Cognitive
The general head space of prochlorperazine is often described as one of sleepiness, emptiness, apathy, stupor and catatonia. The specific cognitive effects can be broken down into several components which progressively intensify proportional to dosage.
Pharmacology
Pharmacodynamics
Prochlorperazine antagonizes D2 dopamine receptors in the brain,1 and also increases dopamine turnover in the brain.5 Its antipsychotic mechanism is not fully established but is thought to depend primarily on dopamine blockade, while D2 blockade in the chemoreceptor trigger zone mediates its antiemetic action. It also antagonizes histamine H1, cholinergic, and alpha-1 and alpha-2 adrenergic receptors, with alpha-1 blockade contributing to muscle relaxation. One study suggests that it may inhibit P2X7 receptors in human macrophages and thereby reduce calcium influx.6
Pharmacokinetics
Prochlorperazine is well absorbed from the gastrointestinal tract,5 although mean oral bioavailability in healthy volunteers was approximately 12.5%. Peak plasma concentrations occurred about 5 hours after oral administration, and repeated twice-daily dosing produced accumulation of the drug and its metabolite, with steady state reached by 7 days. Hepatic metabolism includes oxidation, hydroxylation, demethylation, sulfoxide formation, and glucuronic acid conjugation; CYP2D6 mediates oxidation, and prochlorperazine is also listed as a CYP3A4 substrate. Metabolites have been detected after oral and buccal administration, and the drug may undergo enterohepatic circulation. It distributes widely into tissues, with high concentrations in the liver and spleen; a preliminary intravenous study reported mean apparent distribution volumes of approximately 1401 L and 1548 L after 6.25 mg and 12.5 mg, respectively. Elimination occurs mainly through feces and bile, with small quantities of unchanged drug and metabolite detected in urine. Terminal elimination half-lives were 8 hours after a single oral dose and 9 hours after intravenous administration. In healthy volunteers receiving intravenous prochlorperazine, mean plasma clearance was approximately 0.98 L/hour/kg and mean renal clearance was about 23.6 mL/hour.
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Harm Potential
Addiction & Dependence
Psychological
Psychological dependence can develop with long-term prochlorperazine use.
Physical
Physical dependence can develop with long-term use, and abrupt cessation can trigger withdrawal. Withdrawal commonly includes nausea, vomiting, and reduced appetite; other symptoms include restlessness, sweating, insomnia, and, less commonly, vertigo, numbness, or muscle pain. Third-trimester exposure to antipsychotics, including prochlorperazine, carries a risk of neonatal withdrawal after delivery.9
Toxicity
| Species | Route | Value |
|---|---|---|
| rat | oral | 750 mg/kg |
| mouse | intraperitoneal | 191 mg/kg |
| mouse | subcutaneous | 320 mg/kg |
Prochlorperazine can cause acute dystonia, pseudoparkinsonism, akathisia, and potentially irreversible tardive dyskinesia; longer treatment and greater cumulative exposure are proposed to increase the risk of tardive dyskinesia and its irreversibility. Overdose can cause dystonic reactions and central nervous system depression, including severe drowsiness or coma.10 Third-trimester antipsychotic exposure, including prochlorperazine, can cause neonatal extrapyramidal symptoms after delivery.
Prochlorperazine can cause potentially fatal neuroleptic malignant syndrome, with high fever, muscle rigidity, altered mental status, and autonomic instability.
Prochlorperazine overdose can cause ECG abnormalities, arrhythmias, hypotension, and fainting. Prochlorperazine carries an increased-mortality warning for elderly patients with dementia-related psychosis.3
Prochlorperazine overdose can cause difficulty breathing.11
Prochlorperazine overdose can cause ileus, severe constipation, abdominal pain, and dry mouth.
Prochlorperazine overdose can cause difficulty urinating.11
Psychosis Risk
Tentative evidence links antipsychotic discontinuation to psychosis; stopping treatment may also lead to recurrence of the condition being treated.
Seizure Risk
Prochlorperazine overdose can cause seizures or convulsions.11
History & Culture
Prochlorperazine was developed in the 1950s and approved for medical use in the United States in 1956.12 It remained widely used for nausea and vomiting despite heavier promotion of newer antiemetics, including 5-HT3 antagonists.12…
Legality
By Country
United StatesPrescription only
ItalyPrescription only
AustraliaLegal (regulated)
United KingdomLegal (regulated)References
Citations
Article Status
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