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antipsychotic and antiemetic drug used to treat schizophrenia and to combat nausea and vomiting

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/08 12:25:43」(JST)

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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.^[1] Intravenous administration can be used to treat status migrainosus.

Indications

Prochlorperazine is a phenothiazine drug. Most drugs in this category are used as anti-psychotics (neuroleptics).^[2] 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^[3]
As an antiemetic, particularly for nausea and vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting^[4]
In the UK, prochlorperazine maleate is available as Buccastem M in buccal form as an over-the-counter treatment for migraine.^[5] 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^[6]

Pharmacology

Prochlorperazine is thought to exert its antipsychotic effects by blocking dopamine receptors.^[7]

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

5mg oral tablet of Prochlorperazine

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.^[8]

Side effects

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.^[9]^[10]

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.

References

^ Husseini A, Gianakos D (February 2006). "The 15-Minute Visit". Patient Care 40: 9–10.
^ Casey JF, Lasky JJ, Klett CJ, Hollister LE (August 1960). "Treatment of schizophrenic reactions with phenothiazine derivatives. A comparative study of chlorpromazine, triflupromazine, mepazine, prochlorperazine, perphenazine, and phenobarbital". American Journal of Psychiatry 117: 97–105. doi:10.1176/appi.ajp.117.2.97 (inactive 2015-01-09). PMID 13808146.
^ Benson AJ (June 1969). "Effect of diphenidol and prochlorperazine on semicircular canal function in man". Aerospace Medicine 40 (6): 589–95. PMID 4891872.
^ Gralla RJ, Osoba D, Kris MG, Kirkbride P, Hesketh PJ, Chinnery LW, Clark-Snow R, Gill DP, Groshen S, Grunberg S, Koeller JM, Morrow GR, Perez EA, Silber JH, Pfister DG (September 1999). "Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines". Journal of Clinical Oncology 17 (9): 2971–94. PMID 10561376.
^ Siow HC, Young WB, Silberstein SD (April 2005). "Neuroleptics in headache". Headache 45 (4): 358–71. doi:10.1111/j.1526-4610.2005.05074.x. PMID 15836574.
^ Coatesworth AP (November 2000). "Assessment and treatment of dizziness". Journal of Neurology, Neurosurgery, and Psychiatry 69 (5): 706. doi:10.1136/jnnp.69.5.706. PMC 1763384. PMID 11184241.
^ Manuchair S. Ebadi, Desk reference of clinical pharmacology. 2007
^ "Alexza Announces Agreement to Acquire Symphony Allegro, Including All Rights to AZ-004, AZ-104 and AZ-002" (Press release). Alexza Pharmaceuticals. 2009-06-15. Retrieved 2009-11-29.
^ Brown, Thomas Markham; Stoudemire, Alan (1998). "Antipsychotics". Psychiatric Side Effects of Prescription and Over-The-Counter Medications. American Psychiatric Publishing. p. 1946. ISBN 9780880488686. Retrieved 2013-01-18.
^ Drugs.com

External links

Prochlorperazine. MedlinePlus. U.S. National Library of Medicine. National Institutes of Health.
AZ-001 (Staccato prochlorperazine) (original article) Press release pertaining to phase IIb clinical trial of inhaled prochlorperazine for migraine headache
Prochlorperazine edisylate Injection prescribing information Drugs.com
Prochlorperazine. Hazardous Substances Data Bank (HSDB). U.S. National Library of Medicine. National Institutes of Health.
"Suspicious Behavior". Snap Judgment. Episode 405. Public Radio Exchange and NPR. Retrieved May 19, 2014. The segment "Hands Up" relates an anecdote about the side effects of prochlorperazine.

UpToDate Contents

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1. 成人における片頭痛の急性期治療 acute treatment of migraine in adults
2. 薬物乱用頭痛：治療および予後 medication overuse headache treatment and prognosis
3. 制吐剤の特性 characteristics of antiemetic drugs
4. 小児における片頭痛の急性期治療 acute treatment of migraine in children
5. 回転性めまいの治療 treatment of vertigo

English Journal

The Safety of Prochlorperazine in Children: A Systematic Review and Meta-Analysis.

Lau Moon Lin M1, Robinson PD2, Flank J1,3, Sung L4,5, Dupuis LL6,7,8.
Drug safety.Drug Saf.2016 Feb 16. [Epub ahead of print]
INTRODUCTION: Prochlorperazine is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV). The objective of this review was to describe its safety in children when given for any indication to help define its role for CINV control in children.METHODS: El
PMID 26884326

Acute Treatment Therapies for Pediatric Migraine: A Qualitative Systematic Review.

Patniyot IR1,2, Gelfand AA1,2.
Headache.Headache.2016 Jan;56(1):49-70. doi: 10.1111/head.12746.
OBJECTIVE: We sought to conduct a qualitative systematic review to evaluate the safety and efficacy of available treatments for pediatric patients with migraine or benign primary headache in the emergency department, in an effort to inform future practice.METHODS: Scopus, Medline, and PubMed databas
PMID 26790849

Movement Disorders From the Use of Metoclopramide and Other Antiemetics in the Treatment of Migraine.

Wijemanne S1, Jankovic J1, Evans RW2.
Headache.Headache.2016 Jan;56(1):153-61. doi: 10.1111/head.12712. Epub 2015 Nov 17.
Nausea and vomiting are a frequent accompaniment of migraine and anti-nausea medications are frequently used in its management. The majority of anti-nausea medications that are used in migraine are dopamine receptor blocking agents and therefore have the potential to cause drug-induced movement diso
PMID 26573884

Japanese Journal

Incidence of Nausea and Vomiting Induced by Oxycodone Administered with Prochlorperazine in Japanese Cancer Patients

Journal of Nippon Medical School 82(2), 100-105, 2015
NAID 130005068462

プロクロルペラジン（ノバミン<sup>®</sup>）による光線過敏型薬疹の1例

皮膚の科学 12(3), 199-202, 2013
NAID 130004934289

メルファラン連日・大量投与に伴う悪心・嘔吐に対する‌多剤併用制吐療法の後方視的検討

医療薬学 39(1), 18-24, 2013
NAID 130004502776

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★リンクテーブル★

リンク元	「プロクロルペラジン」
拡張検索	「prochlorperazine maleate」「prochlorperazine mesilate」

「プロクロルペラジン」

Prochlorperazine
Systematic (IUPAC) name
	2-chloro-10-[3-(4-methyl-1-piperazinyl)propyl]-; 10H-phenothiazine
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682116
Pregnancy; category	C (Au, U.S.);
Routes of; administration	Oral, buccal, rectal, IM, IV
Legal status	AU: S3 (Pharmacist only); UK: POM, but packs of 8 buccal tablets for nausea/vomiting associated with migraine are sold as pharmacy medicines; US: ℞-only;
Pharmacokinetic data
Bioavailability	not exactly known, but substantial
Protein binding	91–99%
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
Identifiers
CAS Number	58-38-8
ATC code	N05AB04
PubChem	CID 4917
IUPHAR/BPS	7279
DrugBank	DB00433
ChemSpider	4748
UNII	YHP6YLT61T
KEGG	D00493
ChEBI	CHEBI:8435
ChEMBL	CHEMBL728
Chemical data
Formula	C20H24ClN3S
Molar mass	373.943 g/mol
	SMILES Clc2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(C)CC4 ;
	InChI 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 ; Key:WIKYUJGCLQQFNW-UHFFFAOYSA-N ;
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