Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

, migraines,

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

and

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

. It is a less preferred medication for anxiety. It may be taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, rectally, injection into a vein, or injection into a muscle. Common side effects include sleepiness, blurry vision, low blood pressure, and dizziness. Serious side effects may include movement disorders including

tardive dyskinesia Tardive dyskinesia (TD) is an iatrogenic disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips, which occurs following treatment with medication. Additional mo ...

and

neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, va ...

. Use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is generally not recommended. It is a

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics m ...

which is believed to work by reducing the action of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

in the brain. Prochlorperazine was approved for medical use in the United States in 1956. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2020, it was the 355th most commonly prescribed medication in the United States, with more than 600thousand prescriptions.

Medical uses

Vomiting

Prochlorperazine is used to prevent vomiting caused by

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

and in the pre- and postoperative setting. A 2015 Cochrane review found no differences in efficacy among drugs commonly used for this purpose in emergency rooms.

Migraine

Prochlorperazine, generally by intravenous, is used to treat

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

. Such use is recommended by The American Headache Society. A 2019 systematic review found prochlorperazine was nearly three times more likely than

metoclopramide Metoclopramide is a medication used to treat nausea, vomiting, gastroparesis, and gastroesophageal reflux disease. It is also used to treat migraine headaches. Common side effects include feeling tired, diarrhea, akathisia, and tardive dyski ...

to relieve headache within 60 minutes of administration.

Labyrinthitis

In the UK prochlorperazine maleate has been used for

labyrinthitis Labyrinthitis is inflammation of the labyrinth, a maze of fluid-filled channels in the inner ear. Vestibular neuritis is inflammation of the vestibular nerve (the nerve in the ear that sends messages related to motion and position to the brain) ...

, which includes nausea and

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

Side effects

Sedation is very common, and extrapyramidal side effects are common and include restlessness, dystonic reactions, pseudoparkinsonism, and

akathisia Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those a ...

; the extrapyramidal symptoms can affect 2% of people at low doses, whereas higher doses may affect as many as 40% of people. Prochlorperazine can also cause a life-threatening condition called

(NMS). Some symptoms of NMS include high fever, stiff muscles, neck muscle spasms, confusion, irregular pulse or blood pressure, fast heart rate (tachycardia), sweating, and abnormal heart rhythms (arrhythmias). Research from the Veterans Administration and the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

show injection site reactions. Adverse effects are similar in children.

Warning

The FDA-approved label for prochlorperazine includes a warning for increased risk of mortality in elderly patients with dementia-related psychosis.

Discontinuation

The

British National Formulary The ''British National Formulary'' (BNF) is a United Kingdom (UK) pharmaceutical reference book that contains a wide spectrum of information and advice on prescribing and pharmacology, along with specific facts and details about many medicin ...

recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time. There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.

Pharmacology

Prochlorperazine is thought to exert its

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

effects by blocking dopamine receptors. Prochlorperazine is analogous to

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

; both of these agents antagonize dopaminergic D₂ receptors in various pathways of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. This D₂ blockade results in antipsychotic,

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may ...

and other effects. Hyperprolactinemia is a side effect of

dopamine antagonist A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and have been used in t ...

s as blockade of D₂ receptors within the tuberoinfundibular pathway results in increased plasma levels of

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

due to increased secretion by lactotrophs in the anterior pituitary. Following intramuscular injection, the antiemetic action is evident within 5 to 10 minutes and lasts for three to four hours. Rapid action is also noted after buccal treatment. With oral dosing, the start of action is delayed but the duration is somewhat longer (approximately six hours).

Society and culture

In the United Kingdom, prochlorperazine is available for the treatment of nausea caused by migraine as a tablet dissolved in the mouth, and in Australia as a tablet swallowed whole. In the UK, it is available via a prescription and as a

pharmacy medicine The regulation of therapeutic goods, defined as drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are reg ...

, meaning it does not require a prescription but is only available after talking with a

pharmacist A pharmacist, also known as a chemist in English in the Commonwealth of Nations, Commonwealth English, is a healthcare professional who is knowledgeable about preparation, mechanism of action, clinical usage and legislation of medications in ...

Marketing

Prochlorperazine is available as tablets, suppositories, and in an injectable form. As of September 2017 it was marketed under the trade names Ametil, Antinaus, Buccastem, Bukatel, Chlormeprazine, Chloropernazine, Compazine, Compro, Daolin, Dhaperazine, Emedrotec, Emetiral, Eminorm, Lotamin, Mitil, Mormal, Nautisol, Novamin, Novomit, Proazine, Procalm, Prochlorperazin, Prochlorperazine, Prochlorpérazine, Prochlorperazinum, Prochlozine, Proclorperazina, Promat, Promin, Promtil, Roumin, Scripto-metic, Seratil, Stemetil, Steremal, Vergon, Vestil, and Volimin.

Historical Formulations

Prochlorperazine was combined with

paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...

and marketed for humans as the

combination drug A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

Vestil-A; it was combined with isopropamide (brand name Darbazine) as a combination drug for veterinary use. Until 1981, a combination diet pill composed of prochlorperazine and

dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

was marketed as Eskatrol in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

Smith, Kline & French Smith, Kline & French (SKF) was an American pharmaceutical company that is now a part of the British group GSK plc. History In 1830, John K. Smith opened a drugstore in Philadelphia, and his younger brother, George, joined him in 1841 to form ...

Laboratories.

Research

Alexza Pharmaceuticals studied an inhaled form of prochlorperazine for the treatment of migraine through Phase II trials under the development name AT-001; development was discontinued in 2011.

Synthesis

The alkylation of 2-chlorophenothiazine (1) and 1-(3-Chloropropyl)-4-methylpiperazine 04-16-5(2) in the presence of sodamide gives Prochlorperazine (3); or by alkylation of 2-Chloro-10-(3-chloropropyl)phenothiazine 765-59-5(4) and 1-methylpiperazine (5).

References

External links

* {{Portal bar , Medicine Antiemetics Antimigraine drugs Typical antipsychotics Chloroarenes GHB receptor ligands Hepatotoxins Phenothiazines 4-Methylpiperazin-1-yl compounds Wikipedia medicine articles ready to translate