Prochlorperazine

Last updated
Prochlorperazine
Prochlorperazine.svg
Clinical data
Trade names Compazine, Stemetil, others
AHFS/Drugs.com Monograph
MedlinePlus a682116
License data
Pregnancy
category
  • AU:C
Routes of
administration 		Oral administration, rectal administration, intramuscular injection, intravenous injection (IV)
Drug class Typical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Unknown, but presumed substantial
Protein binding 91–99%
Metabolism Mainly Liver (CYP2D6 and/or CYP3A4)
Elimination half-life 4–8 hours, differs with the method of administration
Excretion Bile duct, (colored) inactive metabolites in urine
Identifiers
  • 2-chloro-10-[3-(4-methyl-1-piperazinyl)propyl]-10H-phenothiazine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.345 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H24ClN3S
Molar mass 373.94 g·mol−1
3D model (JSmol)
  • Clc2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(C)CC4
  • InChI=1S/C20H24ClN3S/c1-22-11-13-23(14-12-22)9-4-10-24-17-5-2-3-6-19(17)25-20-8-7-16(21)15-18(20)24/h2-3,5-8,15H,4,9-14H2,1H3 Yes check.svgY
  • Key:WIKYUJGCLQQFNW-UHFFFAOYSA-N Yes check.svgY
   (verify)

Prochlorperazine, formerly [5] sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. [6] [7] [8] [9] It is a less preferred medication for anxiety. [6] It may be taken by mouth, rectally, injection into a vein, or injection into a muscle. [6]

Contents

Common side effects include sleepiness, blurry vision, low blood pressure, and dizziness. [6] Serious side effects may include movement disorders including tardive dyskinesia and neuroleptic malignant syndrome. [6] Use in pregnancy and breastfeeding is generally not recommended. [10] It is a typical antipsychotic which is believed to work by reducing the action of dopamine in the brain. [6]

Prochlorperazine was approved for medical use in the United States in 1956. [6] It is available as a generic medication. [7] In 2020, it was the 355th most commonly prescribed medication in the United States, with more than 600 thousand prescriptions. [11] [12]

Medical uses

Vomiting

Prochlorperazine is used to prevent vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting. [13] A 2015 Cochrane review found no differences in efficacy among drugs commonly used for this purpose in emergency rooms. [14]

Migraine

Prochlorperazine, generally by intravenous, is used to treat migraine. [15] [16] Such use is recommended by The American Headache Society. [8] A 2019 systematic review found prochlorperazine was nearly three times as likely as metoclopramide to relieve headache within 60 minutes of administration. [15]

Labyrinthitis

In the UK prochlorperazine maleate has been used for labyrinthitis, which include not only nausea and vertigo, but spatial and temporal 'jerking' and distortion. [17]

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. [18] [19]

Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (NMS). Some symptoms of NMS include high fever, stiff muscles, neck muscle spasm, confusion, irregular pulse or blood pressure, fast heart rate (tachycardia), sweating, abnormal heart rhythms (arrhythmias). Research from the Veterans Administration and United States Food and Drug Administration show injection site reactions. Adverse effects are similar in children. [13]

Warning

The FDA approved label for prochlorperazine includes a warning for increased risk of mortality in elderly patients with dementia related psychosis. [20]

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. [21] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. [22] Other symptoms may include restlessness, increased sweating, and trouble sleeping. [22] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. [22] Symptoms generally resolve after a short period of time. [22]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis. [23] It may also result in reoccurrence of the condition that is being treated. [24] Rarely tardive dyskinesia can occur when the medication is stopped. [22]

Pharmacology

Prochlorperazine
Site Ki (nM)SpeciesRef
5-HT1A 5,888Human [25]
5-HT2A 7.24Human [25]
5-HT2C 123Human [25]
5-HT3 1349Human [25]
5-HT6 148Human [25]
5-HT7 6,760Human [25]
α1 24Human [26]
α2 1700Human [26]
M1 776Human [25]
M2 1413Human [25]
D1 251Human [25]
D2 2.24Human [25]
D3 1.82Human [25]
D4 5.37Human [25]
H1 6.03Human [27]
H3 17,378Human [27]
H4 17783Human [27]
DAT 589Human [25]
NET 600Rat [28]

Prochlorperazine is thought to exert its antipsychotic effects by blocking dopamine receptors. [29]

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 3 to 4 hours. Rapid action is also noted after buccal treatment. With oral dosing, the start of action is delayed but the duration somewhat longer (approximately 6 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. [30] [31]

Marketing

Prochlorperazine is available as tablets, suppositories, and in an injectable form. [32]

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. [32] [33]

It was also marketed at that time as a combination drug for humans with paracetamol as Vestil-A, as a combination drug for veterinary use, with isopropamide as Darbazine. [32]

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. [34]

Synthesis

Thieme Synthesis: Patent: Prochlorperazine synthesis.svg
Thieme Synthesis: Patent:

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).

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

<span class="mw-page-title-main">Chlorpromazine</span> Antipsychotic medication

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 disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Fluphenazine</span> Typical antipsychotic medication

Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication. It is used in the treatment of chronic psychoses such as schizophrenia, and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine. It is given by mouth, injection into a muscle, or just under the skin. There is also a long acting injectable version that may last for up to four weeks. Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Risperidone</span> Antipsychotic medication

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. It is taken orally.

<span class="mw-page-title-main">Ziprasidone</span> Antipsychotic medication

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia, obsessive compulsive disorder (OCD), and bipolar disorder; other uses include as an add-on treatment in major depressive disorder, tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Paliperidone</span> Antipsychotic medication

Paliperidone, sold under the trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Iloperidone</span> Atypical antipsychotic medication

Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.

<span class="mw-page-title-main">Zuclopenthixol</span> Typical antipsychotic medication

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

<span class="mw-page-title-main">Perospirone</span> Atypical antipsychotic medication

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

<span class="mw-page-title-main">Lurasidone</span> Atypical antipsychotic medication

Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

<span class="mw-page-title-main">Antipsychotic switching</span> Process of transferring between antipsychotics

Antipsychotic switching refers to the process of switching out one antipsychotic for another antipsychotic. There are multiple indications for switching antipsychotics, including inadequate efficacy and drug intolerance. There are several strategies that have been theorized for antipsychotic switching, based upon the timing of discontinuation and tapering of the original antipsychotic and the timing of initiation and titration of the new antipsychotic. Major adverse effects from antipsychotic switching may include supersensitivity syndromes, withdrawal, and rebound syndromes.

References

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