Metoclopramide - Wikipedia, the free encyclopedia

19/04/15 12:16

Metoclopramide
From Wikipedia, the free encyclopedia

Metoclopramide (INN) /mtklprmad/ is a medication

Metoclopramide

used mostly for stomach and esophageal problems.[1] It

belongs to the group of medications known as dopaminereceptor antagonists.[2]
It is commonly used to treat nausea and vomiting, to help
with emptying of the stomach in people with delayed
stomach emptying due to either diabetes or following surgery,

Systematic (IUPAC) name

and to help with gastroesophageal reflux disease.[2] It is also

used to treat migraine headaches.[3]

4-amino-5-chloro-N-(2-(diethylamino)ethyl)2-methoxybenzamide

Common side effects include: feeling tired, diarrhea and

feeling restless. More serious side effects include: movement
disorder like tardive dyskinesia, a condition called

Clinical data
Trade names

See list

neuroleptic malignant syndrome, and depression.[2] It is thus

rarely recommended that people take the medication for

AHFS/Drugs.com monograph
MedlinePlus

a684035

longer than twelve weeks.[2] It is pregnancy category B in the

United States and category A in Australia, meaning no
evidence of harm has been found after it being taken by many

Licence data

US FDA:link

Pregnancy
category

AU: A
US: B (No risk in non-

pregnant women.[2][4]
In 2012, metoclopramide was one of the top 100 most

human studies)
Legal status

AU: Prescription Only

prescribed medications in the United States.[5] It is on the

World Health Organization's List of Essential Medicines, a
list of the most important medication needed in a basic health

(S4)

system.[6]

US: -only

UK: Prescription-only

(POM)
Routes of
administration

Oral, intravenous, intramuscular

Pharmacokinetic data

Contents

Bioavailability

8015% (oral)

Metabolism

Hepatic

1.1 Antiemetic

Half-life

56 hours

1.2 Gastroprokinetic

Excretion

7085% renal, 2% faecal

1 Medical uses

1.3 Other indications

2 Adverse effects
3 Cautions
3.1 Pregnancy
http://en.wikipedia.org/wiki/Metoclopramide

Identifiers
CAS Registry
Number

364-62-5

ATC code

A03FA01

PubChem

CID 4168
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3.2 Infants

IUPHAR ligand

241

4 Mechanism of action

DrugBank

DB01233

5 Brand names

ChemSpider

4024

6 Veterinary use

UNII

L4YEB44I46

KEGG

D00726

ChEBI

CHEBI:107736

ChEMBL

CHEMBL86

7 Use
8 See also
9 References
10 Further reading

Chemical data

Medical uses
Clinicians commonly use metoclopramide to treat nausea including that due to chemotherapy and that occurring
postoperatively. Evidence also supports its use for
gastroparesis (poor stomach emptying) and gastroesophageal
reflux disease.[2]

Formula

C14H22ClN3O2

Molecular mass

299.80 g/mol

SMILES
InChI
Physical data
Melting point

147.3 C (297.1 F)
(what is this?) (verify)

Antiemetic
Metoclopramide treats nausea and vomiting associated with conditions
such as uremia, radiation sickness, malignancy, labor, infection,
migraine headaches, and emetogenic drugs.[7][8] In the setting of painful
conditions such as migraine headaches, metoclopramide may be used in
combination with paracetamol (acetaminophen) (available in the UK as
Paramax, and in Australia as Metomax), or in combination with aspirin
(MigraMax). It is also used preventatively by some EMS providers
when transporting people who are conscious and spinally
Metoclopramide 5-mg tablets (Pliva)

immobilized.[9]

The Rosemont Patient Information Leaflet of their sugar-free metoclopramide hydrochloride (5 mg/5 ml) oral
solution states, " Metoclopramide can be used to treat stomach upset including heartburn, wind, pain,
indigestion, sickness and bile regurgitation, to stop nausea and vomiting, to relieve your symptoms of nausea
and vomiting when you have a migraine, to help restore normal stomach emptying after an operation and during
hospital tests such as a barium meal." and "In young adults and children, metoclopramide can be given for
severe and long-lasting vomiting if the cause is known, to stop vomiting caused by cancer treatment such as
radiotherapy and chemotherapy, to help in passing a tube into the stomach and intestine and to help stop feeling
and being sick before having an operation." [10]

Gastroprokinetic

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Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric
contractions, and relaxes the pyloric sphincter and duodenal bulb, while simultaneously increasing lower
esophageal sphincter tone. These gastroprokinetic effects make metoclopramide useful in the treatment of
gastric stasis (for example: after gastric surgery or diabetic gastroparesis), as an aid in gastrointestinal
radiographic studies by accelerating transit through the gastrointestinal system in barium studies, and as an aid
in difficult intubation of the small intestine. It is also used in gastroesophageal reflux disease.[11]

Other indications
By inhibiting the action of dopamine, metoclopramide has sometimes been used to stimulate lactation.[12] It can
also help treat migraines.[3]

Adverse effects
Common adverse drug reactions (ADRs) associated with
metoclopramide therapy include restlessness (akathisia), and focal
dystonia. Infrequent ADRs include hypertension, hypotension,
hyperprolactinaemia leading to galactorrhea, constipation, depression,
headache, and extrapyramidal effects such as oculogyric crisis. Rare but
serious ADRs associated with metoclopramide therapy include
agranulocytosis, supraventricular tachycardia, hyperaldosteronism,
neuroleptic malignant syndrome, akathisia and tardive dyskinesia.[8]
Metoclopramide may be the most common cause of drug-induced
disorders.[13]

Plastic ampoule of metoclopramide

movement
The risk of extrapyramidal effects is increased
in people under 20 years of age, and with high-dose or prolonged
therapy.[7][8] Tardive dyskinesia may be persistent and irreversible in some patients. The majority of reports of
tardive dyskinesia occur in people who have used metoclopramide for more than three months.[13]
Consequently, the US Food and Drug Administration (FDA) recommends that metoclopramide be used for
short-term treatment, preferably less than 12 weeks. In 2009, the FDA required all manufacturers of
metoclopramide to issue a black box warning regarding the risk of tardive dyskinesia with chronic or high-dose
use of the drug.[13]
Dystonic reactions may be treated with benzatropine, diphenhydramine, trihexyphenidyl, or procyclidine.
Symptoms usually subside with benadryl (diphenhydramine hydrochloride) or benzatropine injected
intramuscularly.[14] Agents in the benzodiazepine class of drugs may be helpful, but benefits are usually modest
and side effects of sedation and weakness can be problematic.[15]
In some cases, the akathisia effects of metoclopramide are directly related to the infusion rate when the drug is
administered intravenously. Side effects were usually seen in the first 15 minutes after the dose of
metoclopramide.[16]

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Cautions
Metoclopramide is contraindicated in pheochromocytoma. It should be used with caution in Parkinson's disease
since, as a dopamine antagonist, it may worsen symptoms. Long-term use should be avoided in patients with
clinical depression, as it may worsen one's mental state.[8] Also, it is contraindicated in patients with a
suspected bowel obstruction.[2]
Patients with a history of ADHD, restless legs syndrome, hyperprolactinaemia, and Parkinson's disease should
be closely monitored when using dopamine antagonists for treatment of emesis. Patients who take
antipsychotics are recommended not to take metoclopramide.

Pregnancy
Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or
unborn baby.[17] In the USA, it has been assigned to pregnancy category B by the US FDA.[18] A large cohort
study of babies born to Israeli women exposed to metoclopramide during pregnancy found no evidence that the
drug increases the risk of congenital malformations, low birth weight, preterm birth, or perinatal mortality. [19]
A large cohort study in Denmark found, in addition, no association between metoclopramide exposure and
miscarriage.[20] Metoclopramide is excreted into milk.[17]

Infants
A systematic review found a wide range of reported outcomes for treatment of gastroesophageal reflux disease
(GERD) in infants and concluded a "poor" rating of evidence and "inconclusive" rating of safety and efficacy
for the treatment of GERD in infants.[21]

Mechanism of action
Metoclopramide was first described by Dr. Louis Justin-Besanon and C. Laville in 1964.[22]
It appears to bind to dopamine D2 receptors with nanomolar affinity (Ki 28.8 nM),[23] where it is a receptor
antagonist, and is also a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist.
The antiemetic action of metoclopramide is due to its antagonist activity at D2 receptors in the chemoreceptor
trigger zone in the central nervous system this action prevents nausea and vomiting triggered by most
stimuli.[24] At higher doses, 5-HT3 antagonist activity may also contribute to the antiemetic effect.
The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D2 receptor antagonist
activity and 5-HT4 receptor agonist activity.[25][26] The gastroprokinetic effect itself may also contribute to the
antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.[27]

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Brand names
Metoclopramide is available world-wide under various trade names:
Afipran (Takeda Nycomed,[28] Norway)
Maxolon (Shire/Valeant in Australia and the UK)
Cerucal (AWD Pharma)
Clopamon (Aspen, South Africa)[29]
Contromet (Adcock-Ingram, South Africa)
Degan (Lek)
Maxeran (Sanofi)
Pasperan (Syrian Arab Republic)
Plasil (Sanofi)
Plazilin (Iran)

Maxolon 10MG Box, Tablet, Sheet

Pramin (Rafa, Israel)

Primperan (Sanofi)
Pulin (Malaysia)
Pylomid (Bosnalijek)
Reglan (Schwarz Pharma in the USA)
Tomit (Indonesia)
Perinorm (India)
Meclodin (Iraq)

Veterinary use
Metoclopramide is also commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant
in rabbits.[30]

Use
Metoclopramide is contraindicated in case of epilepsy, if a stomach operation has been performed in the
previous three or four days, if the patient has ever had bleeding, perforation or blockage of the stomach, in cases
of pheochromocytoma, and in newborn babies.[10]

See also
Benzamide, the chemical class to which metoclopramide belongs

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Bromopride, the bromo- analogue of metoclopramide

Cisapride, a benzamide with a different mechanism of action
Itopride, a newer benzamide with effects similar to those of metoclopramide

References
1. "Metoclopramide" (http://www.nlm.nih.gov/medlineplus/druginfo/meds/a684035.html). nlm.nih.gov. Retrieved
28 September 2014.
2. "Metoclopramide hydrochloride" (http://www.drugs.com/monograph/metoclopramide-hydrochloride.html). Monograph.
The American Society of Health-System Pharmacists. Retrieved 2014-09-27.
3. Derry, S; Moore, RA; McQuay, HJ (Nov 10, 2010). "Paracetamol (acetaminophen) with or without an antiemetic for
acute migraine headaches in adults.". The Cochrane database of systematic reviews (11): CD008040.
doi:10.1002/14651858.CD008040.pub2 (https://dx.doi.org/10.1002%2F14651858.CD008040.pub2). PMID 21069700
(https://www.ncbi.nlm.nih.gov/pubmed/21069700).
4. "Prescribing medicines in pregnancy database" (http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw).
Australian Government. 3 March 2014. Retrieved 22 April 2014.
5. Bartholow, Michael. "Top 200 Drugs of 2012" (http://www.pharmacytimes.com/publications/issue/2013/July2013/Top200-Drugs-of-2012). Pharmacy Times. Retrieved 22 April 2014.
6. "WHO Model List of EssentialMedicines" (http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1)
(PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

7. "Maxolon (Australian Approved Product Information)" (http://www.mydr.com.au/medicines/cmis/maxolon-tablets).

Valeant Pharmaceuticals. 2000.
8. Rossi S., ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3.
9. "Ambulance Victoria Clinical Guideline A0701"http://www.ambulance.vic.gov.au/media/docs/Adult%20CPG%20wma01f0e1e-4fc0-405c-bc83-3136adf4a723-0.pdf
10. http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068
11. "METOCLOPRAMIDE (metoclopramide hydrochloride) injection, solution [Hospira, Inc.]"
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=373ba08b-33ad-49fc-28a7-928e89a65314#nlm34089-3
12. "Metoclopramide" (http://www.lowmilksupply.org/metoclopramide.shtml). lowmilksupply.org.
13. "FDA requires boxed warning and risk mitigation strategy for metoclopramide-containing drugs"
(http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149533.htm) (Press release). U.S. Food and
Drug Administration. 2009-02-26. Retrieved 2009-06-11. "Lay Summary WebMD"
(http://www.webmd.com/digestive-disorders/news/20090227/metoclopramide-drugs-get-black-box-warning).
14. "Metoclopramide (metoclopramide hydrochloride) injection, solution [Hospira, Inc.]"
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=373ba08b-33ad-49fc-28a7-928e89a65314#nlm34089-3
15. Olanow C, Schapira AV. Chapter 372. Parkinson's Disease and Other Movement Disorders. In: Longo DL, Fauci AS,
Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY:
McGraw-Hill; 2012.
16. Parlak, I; Atilla, R; Cicek, M; Parlak, M; Erdur, B; Guryay, M; Sever, M; Karaduman, S (Sep 2005). "Rate of
metoclopramide infusion affects the severity and incidence of akathisia."
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(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1726928). Emergency medicine journal : EMJ 22 (9): 6214.

doi:10.1136/emj.2004.014712 (https://dx.doi.org/10.1136%2Femj.2004.014712). PMC 1726928
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1726928). PMID 16113179
(https://www.ncbi.nlm.nih.gov/pubmed/16113179).
17. Briggs, G. G.; Freeman, R. K.; Yaffe, S. J. (2008). Drugs in Pregnancy and Lactation (http://books.google.com/books?
id=YOEV2w3XTxsC&pg=PA1197) (8th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 11971200. ISBN 07817-7876-X. Retrieved 2009-06-11.
18. http://www.drugs.com/metoclopramide.html
19. Matok, I.; Gorodischer, R.; Koren, G.; Sheiner, E.; Wiznitzer, A.; Levy, A. (2009). "The Safety of Metoclopramide Use
in the First Trimester of Pregnancy" (http://www.nejm.org/doi/pdf/10.1056/NEJMoa0807154) (PDF). New England
Journal of Medicine 360 (24): 25282535. doi:10.1056/NEJMoa0807154
(https://dx.doi.org/10.1056%2FNEJMoa0807154). PMID 19516033 (https://www.ncbi.nlm.nih.gov/pubmed/19516033).
20. Pasternak, B. R.; Svanstrm, H.; Mlgaard-Nielsen, D.; Melbye, M.; Hviid, A. (2013). "Metoclopramide in Pregnancy
and Risk of Major Congenital Malformations and Fetal Death". JAMA 310 (15): 16011611.
doi:10.1001/jama.2013.278343 (https://dx.doi.org/10.1001%2Fjama.2013.278343). PMID 24129464
(https://www.ncbi.nlm.nih.gov/pubmed/24129464).
21. Hibbs, AM; Lorch, SA (Aug 2006). "Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a
systematic review.". Pediatrics 118 (2): 74652. doi:10.1542/peds.2005-2664 (https://dx.doi.org/10.1542%2Fpeds.20052664). PMID 16882832 (https://www.ncbi.nlm.nih.gov/pubmed/16882832).
22. Justin-Besancon, L.; Laville, C. (1964). "Antiemetic Action of Metoclopramide with Respect to Apomorphine and
Hydergine". Comptes Rendus des Sances de la Socit de Biologie et de ses Filiales (in French) 158: 723727.
PMID 14186927 (https://www.ncbi.nlm.nih.gov/pubmed/14186927).
23. Prediction of Catalepsies Induced by Amiodarone, Aprindine and Procaine: Similarity in Conformation of
Diethylaminoethyl Side Chain http://jpet.aspetjournals.org/content/287/2/725.full.pdf
24. Rang, H. P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone.
ISBN 0-443-07145-4.
25. Sweetman S., ed. (2004). Martindale: The Complete Drug Reference (34th ed.). London: Pharmaceutical Press. ISBN 085369-550-4.
26. Tonini, M.; Candura, S. M.; Messori, E.; Rizzi, C. A. (1995). "Therapeutic Potential of Drugs with Mixed 5-HT4
Agonist/5-HT3 Antagonist Action in the Control of Emesis". Pharmacological Research 31 (5): 257260. ISSN 10436618 (https://www.worldcat.org/issn/1043-6618). PMID 7479521 (https://www.ncbi.nlm.nih.gov/pubmed/7479521).
27. Feldman, M.; Friedman, L. S.; Brandt, L. J., eds. (2010). "Ch. 43: Gastroesophageal Reflux Disease". Sleisenger and
Fordtran's Gastrointestinal and Liver Disease (9th ed.). Philadelphia: Saunders. ISBN 978-1-4160-6189-2.
28. felleskatalogen.no
29. Snyman, J.R., ed. (June 2010). MIMS (Monthly Index of Medical Specialities) (Vol. 50 no. 6 ed.). Johannesburg: Avusa
Media Ltd.
30. Mikota, S. K.; Plumb, D. C. (June 2003). "Metoclopramide HCl" (http://www.elephantcare.org/Drugs/metoclop.htm).
The Elephant Formulary. Elephant Care International.

Further reading
http://en.wikipedia.org/wiki/Metoclopramide

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Brenner, G. M. (2000). Pharmacology. London: Saunders. ISBN 0-7216-7757-6.

Compendium of Pharmaceuticals and Specialties 2011. Toronto: Canadian Pharmacists Association.
2011. ISBN 978-1-894402-54-5.
Anderson, E. P.; Freeman, E. B. (May 2004). "Recognition of Movement Disorders and Extrapyramidal
side effects - would you recognize them if you see them?"
(http://www.reflux.org/reflux/webdoc01.nsf/487b3ba0c2f1a4ff85256ff30009f061/fdb3ea9e635ff41d8525
702e001b6f6b/$FILE/Tardive%20PGMay04Article.pdf) (PDF). Practical Gastroenterology: 14.
Retrieved from "http://en.wikipedia.org/w/index.php?title=Metoclopramide&oldid=654246742"
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