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| Clinical data | |
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| Trade names | Compazine, Stemetil, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682116 |
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| Routes of administration | Oral administration,rectal administration,intramuscular injection,intravenous injection (IV) |
| Drug class | Typical antipsychotic |
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| Pharmacokinetic data | |
| Bioavailability | Unknown, but presumed substantial |
| Protein binding | 91–99% |
| Metabolism | MainlyLiver (CYP2D6 and/orCYP3A4) |
| Eliminationhalf-life | 4–8 hours, differs with the method of administration |
| Excretion | Bile duct, (colored) inactive metabolites in urine |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.345 |
| Chemical and physical data | |
| Formula | C20H24ClN3S |
| Molar mass | 373.94 g·mol−1 |
| 3D model (JSmol) | |
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Prochlorperazine, formerly[4] sold under the brand nameCompazine among others, is a medication used to treatnausea,migraines,schizophrenia,psychosis andanxiety.[5][6][7][8] It is a less preferred medication for anxiety.[5] It may be takenby mouth,rectally,injection into a vein, orinjection into a muscle.[5]
Common side effects include sleepiness, blurry vision,low blood pressure, and dizziness.[5] Serious side effects may include movement disorders includingtardive dyskinesia andneuroleptic malignant syndrome.[5] Use inpregnancy andbreastfeeding is generally not recommended.[9] It is atypical antipsychotic which is believed to work by reducing the action ofdopamine in the brain.[5]
Prochlorperazine was approved for medical use in the United States in 1956.[5] It is available as ageneric medication.[6] In 2020, it was the 355th most commonly prescribed medication in the United States, with more than 600 thousand prescriptions.[10][11]
Prochlorperazine is used toprevent vomiting caused bychemotherapy,radiation therapy andin the pre- and postoperative setting.[12] A 2015 Cochrane review found no differences in efficacy among drugs commonly used for this purpose in emergency rooms.[13]
Prochlorperazine, generally by intravenous, is used to treatmigraine.[14][15] Such use is recommended by The American Headache Society.[7] A 2019 systematic review found prochlorperazine was nearly three times more likely thanmetoclopramide to relieve headache within 60 minutes of administration.[14]
In the UK prochlorperazine maleate has been used forlabyrinthitis, which includes nausea andvertigo.[16]
Sedation is very common, andextrapyramidal side effects are common and include restlessness,dystonic reactions,pseudoparkinsonism, andakathisia; the extrapyramidal symptoms can affect 2% of people at low doses, whereas higher doses may affect as many as 40% of people.[17][18]
Prochlorperazine can also cause a life-threatening condition calledneuroleptic 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 StatesFood and Drug Administration show injection site reactions. Adverse effects are similar in children.[12]
The FDA-approved label for prochlorperazine includes a warning for increased risk of mortality in elderly patients with dementia-related psychosis.[19]
TheBritish National Formulary recommends a gradual withdrawal whendiscontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[20] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[21] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[21] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[21] Symptoms generally resolve after a short period of time.[21]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[22] It may also result in reoccurrence of the condition that is being treated.[23] Rarely tardive dyskinesia can occur when the medication is stopped.[21]
| Site | Ki (nM) | Species | Ref |
|---|---|---|---|
| 5-HT1A | 5,888 | Human | [24] |
| 5-HT2A | 7.24 | Human | [24] |
| 5-HT2C | 123 | Human | [24] |
| 5-HT3 | 1349 | Human | [24] |
| 5-HT6 | 148 | Human | [24] |
| 5-HT7 | 6,760 | Human | [24] |
| α1 | 24 | Human | [25] |
| α2 | 1700 | Human | [25] |
| M1 | 776 | Human | [24] |
| M2 | 1413 | Human | [24] |
| D1 | 251 | Human | [24] |
| D2 | 2.24 | Human | [24] |
| D3 | 1.82 | Human | [24] |
| D4 | 5.37 | Human | [24] |
| H1 | 6.03 | Human | [26] |
| H3 | 17,378 | Human | [26] |
| H4 | 17783 | Human | [26] |
| DAT | 589 | Human | [24] |
| NET | 600 | Rat | [27] |
Prochlorperazine is thought to exert itsantipsychotic effects by blockingdopamine receptors.[28]
Prochlorperazine is analogous tochlorpromazine; both of these agents antagonize dopaminergicD2 receptors in various pathways of thecentral nervous system. This D2 blockade results in antipsychotic,antiemetic and other effects.Hyperprolactinemia is a side effect ofdopamine antagonists as blockade of D2 receptors within thetuberoinfundibular pathway results in increased plasma levels ofprolactin 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).
In the United Kingdom, prochlorperazine is available for the treatment of nausea caused by migraine as atablet dissolved in the mouth, and in Australia as a tablet swallowed whole. In the UK, it is available via a prescription and as apharmacy medicine, meaning it does not require a prescription but is only available after talking with apharmacist.[29][30]
Prochlorperazine is available as tablets, suppositories, and in an injectable form.[31]
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.[31][32]
Prochlorperazine was combined withparacetamol and marketed[when?] for humans as thecombination drug Vestil-A; it was combined withisopropamide (brand name Darbazine) as a combination drug for veterinary use.[31]
Until 1981, a combinationdiet pill composed of prochlorperazine anddextroamphetamine was marketed asEskatrol in theUnited States bySmith, Kline & French Laboratories.
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.[33]
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).
Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
