|Systematic (IUPAC) name|
|Oral, buccal, rectal, IM, IV|
|Bioavailability||not exactly known, but substantial|
|Metabolism||Mainly hepatic (CYP2D6 and/or CYP3A4)|
|Biological half-life||4–8 hoursS, differs with the method of administration|
|Excretion||Biliary, (colored) inactive metabolites in urine|
|Molar mass||373.943 g/mol|
Prochlorperazine (Compazine, Stemzine, Buccastem, Stemetil, Phenotil) is a dopamine (D2) receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly potent typical antipsychotic, 10–20 times more potent than chlorpromazine. It is also used to treat migraine headaches. Intravenous administration can be used to treat status migrainosus.
Prochlorperazine is a phenothiazine drug. Most drugs in this category are used as anti-psychotics (neuroleptics). Neuroleptic means "nerve seizing", and describes the semi-paralyzing effect these drugs have on the brain and nervous system. Stemetil is no longer being manufactured for sale in Canada as an anti-psychotic, but it is still available for treatment of nausea.
It is now relatively seldom used for the treatment of psychosis and the manic phase of bipolar disorder. It has a prominent antiemetic/antivertiginoic activity and is most often used for the (short-time) treatment of nausea and vomiting and vertigo as follows:
- To alleviate the symptoms of vertigo
- As an antiemetic, particularly for nausea and vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting
- In the UK, prochlorperazine maleate is available as Buccastem M in buccal form as an over-the-counter treatment for migraine. In this indication it blocks the chemoreceptor trigger zone (CTZ) in the brain, which is responsible for causing severe nausea and vomiting. Its over the counter (OTC) use is strictly restricted to a maximum of 2 days, because of the potentially severe side effects of prochlorperazine, which mandate supervision by a health care provider.
- In the UK prochlorperazine maleate has been prescribed to alleviate the symptoms of labyrinthitis, which include not only nausea and vertigo, but spatial and temporal 'jerking' and distortion
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. Hyperprolactinaemia 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.
Formulations and pharmacokinetics
Prochlorperazine is available as an oral liquid, tablets, cream for trans dermal (compounding pharmacy), and suppositories, as well as in an injectable form.
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).
It is available in Egypt under the brand name Emedrotec buccal adhesive tablets by Eva pharma.
There is an inhaled form of prochlorperazine under development by Alexza Pharmaceuticals, currently (November 2009 at the time of writing) in Phase II clinical trials.
Nervous system side effects have been associated with the use of prochlorperazine. Extrapyramidal side effects such as acute dystonic reactions, pseudoparkinsonism, or akathisia can affect 2% of patients at low doses, whereas higher doses may affect as many as 40% of patients.
Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (NMS). Some symptoms of NMS include: high fever, stiff muscles, confusion, irregular pulse or blood pressure, fast heart rate (tachycardia), sweating, irregular heart rhythms (arrhythmias). VA and FDA research shows injection site reaction.
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