マレイン酸プロクロルペラジン

関: prochlorperazine、prochlorperazine mesilate

WordNet

a salt or ester of maleic acid; used as a nontricyclic antidepressant drug for psychomotor activation
antipsychotic and antiemetic drug used to treat schizophrenia and to combat nausea and vomiting

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/02 16:28:38」(JST)

wiki en

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× more potent than chlorpromazine. It is also used to treat migraine headaches. 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).^[1] 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^[2]
As an antiemetic, particularly for nausea and vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting^[3]
In the UK, prochlorperazine maleate is available as Buccastem M in buccal form as an over-the-counter treatment for migraine.^[4] In this indication it blocks the chemoreceptor trigger zone (CTZ) in the brain, which is responsible for causing severe nausea and vomiting. Its 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^[5]

Pharmacology

Prochlorperazine is thought to exert its antipsychotic effects by blocking dopamine receptors.^[6]

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.

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^[when?] in Phase II clinical trials.^[7]

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.^[8]^[9]

Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (NMS). Some symptoms of NMS include: A high fever, stiff muscles, confusion, irregular pulse or blood pressure, a fast heart rate (tachycardia), sweating, irregular heart rhythms (arrhythmias). VA and FDA research shows injection site reaction.

Chemistry

Prochlorpherazine (2-chloro-10-[3-(4-methyl-1-piperazinyl) propyl]-phenothiazine) is prepared by the alkylation of 2-chlorophenothiazine using 4-methyl-1-piperazinyl)propyl-3-chloride in the presence of sodamide, or alkylation of 2-chloro-10-[(3-chloropropyl)]phenothiazine using 1-methylpiperazine.^[10]^[11]^[12]^[13]

References

^ 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 2010-03-18). 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 et al. (September 1999). "Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines". Journal of Clinical Oncology 17 (9): 2971–94. PMID 10561376. Retrieved 2009-06-21.
^ 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. Retrieved 2013-01-18.
^ Drugs.com
^ R.J. Horclois, U.S. Patent 2,902,484 (1959)
^ R.J. Horclois, GB 780193 (1957)
^ R.J. Horclois, DE 1037461 (1955)
^ R.J. Horclois, FR 1167627 (1959)

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. http://snapjudgment.org/Suspicious-Behavior. Retrieved May 19, 2014. The segment "Hands Up" relates an anecdote about the side effects of prochlorperazine.

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English Journal

Acute Migraine Treatment in Adults.

Becker WJ1.
Headache.Headache.2015 Apr 15. doi: 10.1111/head.12550. [Epub ahead of print]
There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature
PMID 25877672

Novel management of postoperative pain using only oral analgesics after LADG.

Mikami J1, Takiguchi S, Miyazaki Y, Takahashi T, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Mori M, Doki Y.
Surgery today.Surg Today.2015 Mar 24. [Epub ahead of print]
PURPOSE: Managing postoperative pain is important to ensure a good quality of life and fast recovery after surgery. We examined the feasibility of peroral management for the postoperative pain after laparoscopic-assisted distal gastrectomy (LADG).METHODS: Between June 2012 and September 2013, we enr
PMID 25801850

Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings.

Orr SL1, Aubé M2, Becker WJ3, Davenport WJ4, Dilli E5, Dodick D6, Giammarco R7, Gladstone J8, Leroux E9, Pim H9, Dickinson G10, Christie SN10.
Cephalalgia : an international journal of headache.Cephalalgia.2015 Mar;35(3):271-84. doi: 10.1177/0333102414535997. Epub 2014 May 29.
BACKGROUND: There is a considerable amount of practice variation in managing migraines in emergency settings, and evidence-based therapies are often not used first line.METHODS: A peer-reviewed search of databases (MEDLINE, Embase, CENTRAL) was carried out to identify randomized and quasi-randomized
PMID 24875925

Japanese Journal

Quantification of prochlorperazine maleate in human plasma by liquid chromatography-mass spectrometry : Application to a bioequivalence study

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 877(27), 3243-3247, 2009-10-01
NAID 10028025703

Coloration of Phenothiazines with Metal-containing Drugs

藥學雜誌 = Journal of the Pharmaceutical Society of Japan 124(9), 587-598, 2004-09-01
NAID 110003614990

A Simple Spectrophotometric Determination of Some Phenothiazine Drugs in Pharmaceutical Samples

Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 16(11), 1127-1131, 2000-11-10
NAID 10006675852

「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 cat.	C (Au, U.S.);
Legal status	AU: Prescription Only (S4); US: ℞-only; OTC/POM (UK);
Routes	Oral, buccal, rectal, IM
Pharmacokinetic data
Bioavailability	not exactly known, but substantial
Protein binding	91–99%
Metabolism	Mainly hepatic (CYP2D6 and/or CYP3A4)
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
DrugBank	DB00433
ChemSpider	4748
UNII	YHP6YLT61T
KEGG	D00493
ChEBI	CHEBI:8435
ChEMBL	CHEMBL728
Chemical data
Formula	C20H24ClN3S
Mol. 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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　　[★]

英: prochlorperazine
化: マレイン酸プロクロルペラジン prochlorperazine maleate, メシル酸プロクロルペラジン prochlorperazine mesilate
商: ノバミン
関: Compazine

「prochlorperazine mesilate」

　　[★]

メシル酸プロクロルペラジン

関: prochlorperazine、prochlorperazine maleate

「マレイン酸プロクロルペラジン」

　　[★]

英: prochlorperazine maleate
関: プロクロルペラジン

「maleate」

　　[★]

マレイン酸、マレイン酸塩、マレイン酸エステル

関: maleic acid

maleic acid

「prochlorperazine」

　　[★] プロクロルペラジン　

[1] 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 2010-03-18). PMID 13808146.

[2] Benson AJ (June 1969). "Effect of diphenidol and prochlorperazine on semicircular canal function in man". Aerospace Medicine 40 (6): 589–95. PMID 4891872.

[3] Gralla RJ, Osoba D, Kris MG et al. (September 1999). "Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines". Journal of Clinical Oncology 17 (9): 2971–94. PMID 10561376. Retrieved 2009-06-21.

[4] 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.

[5] 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.

[6] Manuchair S. Ebadi, Desk reference of clinical pharmacology. 2007

[7] "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.

[8] Brown, Thomas Markham; Stoudemire, Alan (1998). "Antipsychotics". Psychiatric Side Effects of Prescription and Over-The-Counter Medications. American Psychiatric Publishing. p. 1946. Retrieved 2013-01-18.

[9] Drugs.com

[10] R.J. Horclois, U.S. Patent 2,902,484 (1959)

[11] R.J. Horclois, GB 780193 (1957)

[12] R.J. Horclois, DE 1037461 (1955)

[13] R.J. Horclois, FR 1167627 (1959)

リンク元	「プロクロルペラジン」「prochlorperazine mesilate」「マレイン酸プロクロルペラジン」
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prochlorperazine maleate