Prochlorperazine

Prochlorperazine, formerly<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety.<ref name=AHFS2019/><ref name=BNF76>Template:Cite book</ref><ref name=AHS2016>Template:Cite journal</ref><ref name="pmid30725768">Template:Cite book</ref> It is a less preferred medication for anxiety.<ref name=AHFS2019/> It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.<ref name=AHFS2019/>

Common side effects include sleepiness, blurry vision, low blood pressure, and dizziness.<ref name=AHFS2019/> Serious side effects may include movement disorders including tardive dyskinesia and neuroleptic malignant syndrome.<ref name=AHFS2019/> Use in pregnancy and breastfeeding is generally not recommended.<ref name=Preg2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is a typical antipsychotic which is believed to work by reducing the action of dopamine in the brain.<ref name=AHFS2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Prochlorperazine was approved for medical use in the United States in 1956.<ref name=AHFS2019/> It is available as a generic medication.<ref name=BNF76/> In 2020, it was the 355th most commonly prescribed medication in the United States, with more than 600Template:Nbspthousand prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Vomiting

Prochlorperazine is used to prevent vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting.<ref name=Lin2016>Template:Cite journal</ref> A 2015 Cochrane review found no differences in efficacy among drugs commonly used for this purpose in emergency rooms.<ref>Template:Cite journal</ref>

Migraine

Prochlorperazine, generally by intravenous, is used to treat migraine.<ref name="somestats">Template:Cite journal</ref><ref>Template:Cite journal</ref> Such use is recommended by The American Headache Society.<ref name=AHS2016/> A 2019 systematic review found prochlorperazine was nearly three times more likely than metoclopramide to relieve headache within 60 minutes of administration.<ref name="somestats"/>

Labyrinthitis

In the UK prochlorperazine maleate has been used for labyrinthitis, which includes nausea and vertigo.<ref>Template:Cite journal</ref>

Side effects

Sedation is very common, and extrapyramidal side effects are common and include restlessness, dystonic reactions, pseudoparkinsonism, and akathisia; the extrapyramidal symptoms can affect 2% of people at low doses, whereas higher doses may affect as many as 40% of people.<ref name=Brown1998>Template:Cite book</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (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 show injection site reactions. Adverse effects are similar in children.<ref name=Lin2016/>

Warning

The FDA-approved label for prochlorperazine includes a warning for increased risk of mortality in elderly patients with dementia-related psychosis.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">Template:Cite book</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>Template:Cite book</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>Template:Cite journal</ref> It may also result in reoccurrence of the condition that is being treated.<ref>Template:Cite book</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>

Pharmacology

Prochlorperazine

Site	Ki (nM)	Species	Ref
5-HT1A	5,888	Human	<ref name=":0">Template:Cite journal</ref>
5-HT2A	7.24	Human	<ref name=":0" />
5-HT2C	123	Human	<ref name=":0" />
5-HT3	1349	Human	<ref name=":0" />
5-HT6	148	Human	<ref name=":0" />
5-HT7	6,760	Human	<ref name=":0" />
α1	24	Human	<ref name=":1">Template:Cite journal</ref>
α2	1700	Human	<ref name=":1" />
M1	776	Human	<ref name=":0" />
M2	1413	Human	<ref name=":0" />
D1	251	Human	<ref name=":0" />
D2	2.24	Human	<ref name=":0" />
D3	1.82	Human	<ref name=":0" />
D4	5.37	Human	<ref name=":0" />
H1	6.03	Human	<ref name=":2">Template:Cite journal</ref>
H3	17,378	Human	<ref name=":2" />
H4	17783	Human	<ref name=":2" />
DAT	589	Human	<ref name=":0" />
NET	600	Rat	<ref>Template:Cite journal</ref>

Prochlorperazine is thought to exert its antipsychotic effects by blocking dopamine receptors.<ref>Template:Cite book</ref>

Prochlorperazine is analogous to chlorpromazine; both of these agents antagonize dopaminergic D₂ receptors in various pathways of the central nervous system. This D₂ blockade results in antipsychotic, antiemetic and other effects. Hyperprolactinemia is a side effect of dopamine antagonists as blockade of D₂ receptors within the tuberoinfundibular pathway results in increased plasma levels of prolactin 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, meaning it does not require a prescription but is only available after talking with a pharmacist.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Marketing

Prochlorperazine is available as tablets, suppositories, and in an injectable form.<ref name=brands/>

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.<ref name=brands>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Historical Formulations

Prochlorperazine was combined with paracetamol and marketedTemplate:When? for humans as the combination drug Vestil-A; it was combined with isopropamide (brand name Darbazine) as a combination drug for veterinary use.<ref name=brands/>

Until 1981, a combination diet pill composed of prochlorperazine and dextroamphetamine was marketed as Eskatrol in the United States by Smith, Kline & French 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.<ref>Template:Cite journal</ref>

Synthesis

File:Prochlorperazine synthesis.svg

{{US patent|123456|link text}}}} (1959 to Rhone Poulenc Sa).</ref>

The alkylation of 2-chlorophenothiazine (1) and 1-(3-Chloropropyl)-4-methylpiperazine [104-16-5] (2) in the presence of sodamide gives Prochlorperazine (3); or by alkylation of 2-Chloro-10-(3-chloropropyl)phenothiazine [2765-59-5] (4) and 1-methylpiperazine (5).

External links

• {{#invoke:citation/CS1|citation

|CitationClass=web }}