|Systematic (IUPAC) name|
|Pregnancy cat.||A (AU) B (US)|
|Legal status||Prescription Only (S4) (AU) POM (UK) ℞-only (US)|
|Routes||Oral, intravenous, intramuscular|
|Excretion||70–85% renal, 2% faecal|
|Mol. mass||299.80 g/mol|
|Melt. point||147.3 °C (297 °F)|
| (what is this?)
Metoclopramide (INN) (pron.: //) is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.
Medical uses 
Clinicians commonly use metoclopramide to treat nausea - including that due to chemotherapy and that occurring post-operatively. Evidence also supports its use for gastroparesis (poor stomach emptying) and gastroesophageal reflux disease.
Metoclopramide can treat nausea and vomiting associated with conditions such as uremia, radiation sickness, malignancy, labor, infection, migraine headaches, and emetogenic drugs. 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).
Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb. 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 (GERD).
Other indications 
By inhibiting the action of dopamine, metoclopramide has sometimes been used to stimulate lactation. It can also help treat migraines in the setting of allodynia, where it is more effective than triptans.
Adverse effects 
Common adverse drug reactions (ADRs) associated with metoclopramide therapy include restlessness (akathisia), drowsiness, dizziness, fatigue, 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.
Metoclopramide may be the most common cause of drug-induced movement disorders. The risk of extrapyramidal effects is increased in people under 20 years of age, and with high-dose or prolonged therapy. 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. Consequently, the USFDA recommends that metoclopramide be used for short term treatment, preferably less than 12 weeks. In 2009, the USFDA 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.
Mechanism of action 
Metoclopramide was first described by Dr. Louis Justin-Besançon and C. Laville in 1964.
The antiemetic action of metoclopramide is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)—this action prevents nausea and vomiting triggered by most stimuli. 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. The gastroprokinetic effect itself may also contribute to the antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.
Contraindications and precautions 
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 mental state. Also contraindicated with a suspected bowel obstruction.
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.
Use in pregnancy 
Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or unborn baby. In the USA, it has been assigned to pregnancy category B by the FDA. 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.  Metoclopramide is excreted into milk.
Brand names 
It is available under various trade names including Maxolon in Australia and the UK (Shire/Valeant), Reglan in the USA (Schwarz Pharma), Degan (Lek), Maxeran (Sanofi Aventis), Primperan (Sanofi Aventis), Pylomid (Bosnalijek), Plazilin (Iran), "'Tomit'" (Indonesia), Cerucal (AWD Pharma), Pramin (Rafa, Israel)), Plasil (Sanofi Aventis), Pulin(Malaysia) , Pasperan (Syrian Arab Republic)
Veterinary use 
Metoclopramide is also used in animals. It is commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.
See also 
- Benzamide, the chemical class to which metoclopramide belongs
- "Metoclopramide hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 2011-04-03.
- "Maxolon (Australian Approved Product Information)". Valeant Pharmaceuticals. 2000.
- Rossi S., ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3.
- "Metoclopramide". lowmilksupply.org.
- Snow, V.; Weiss, K.; Wall, E. M.; Mottur-Pilson, C.; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine (2002). "Pharmacologic Management of Acute Attacks of Migraine and Prevention of Migraine Headache" (pdf). Annals of Internal Medicine 137 (10): 840–849. PMID 12435222.
- "FDA requires boxed warning and risk mitigation strategy for metoclopramide-containing drugs" (Press release). U.S. Food and Drug Administration. 2009-02-26. Retrieved 2009-06-11. "Lay Summary – WebMD".
- Justin-Besancon, L.; Laville, C. (1964). "Antiemetic Action of Metoclopramide with Respect to Apomorphine and Hydergine". Comptes Rendus des Séances de la Société de Biologie et de ses Filiales (in French) 158: 723–727. PMID 14186927.
- Rang, H. P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.
- Sweetman S., ed. (2004). Martindale: The Complete Drug Reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4.
- 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): 257–260. ISSN 1043-6618. PMID 7479521.
- 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.
- Briggs, G. G.; Freeman, R. K.; Yaffe, S. J. (2008). Drugs in Pregnancy and Lactation (8th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 1197–1200. ISBN 0-7817-7876-X. Retrieved 2009-06-11.
- Matok, I.; Gorodischer, R.; Koren, G.; Sheiner, E.; Wiznitzer, A.; Levy, A. (2009). "The Safety of Metoclopramide Use in the First Trimester of Pregnancy" (pdf). New England Journal of Medicine 360 (24): 2528–2535. doi:10.1056/NEJMoa0807154. PMID 19516033.
- Mikota, S. K.; Plumb, D. C. (2003-06). "Metoclopramide HCl". The Elephant Formulary. Elephant Care International.
Further reading 
- 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?" (pdf). Practical Gastroenterology: 14.