Identification

Name
Metoclopramide
Accession Number
DB01233
Description

Diabetic gastroparesis is a condition that causes frequent nausea and vomiting, which has a negative impact on quality of life and poses a significant burden on the healthcare system.6 Metoclopramide is a dopamine antagonist used to treat nausea and vomiting that may be associated with diabetic gastroparesis in addition to gastroesophageal reflux disease (GERD). It can also be used to prevent nausea or vomiting associated with chemotherapy or certain surgical or diagnostic procedures.19

One unique property of this drug is that it does not increase gastric acid secretion. It is available in the oral tablet form or in solution, and can also be administered through the intravenous route.17 Metoclopramide was initially approved by the FDA in 1980.5

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 299.796
Monoisotopic: 299.14005467
Chemical Formula
C14H22ClN3O2
Synonyms
  • 2-methoxy-4-amino-5-chloro-N,N-(dimethylaminoethyl)benzamide
  • 2-methoxy-5-chloroprocainamide
  • 4-amino-5-chloro-2-methoxy-N-(β-diethylaminoethyl)benzamide
  • 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-o-anisamide
  • Metoclopramida
  • Metoclopramide
  • Metoclopramidum
External IDs
  • DEL 1267

Pharmacology

Indication

Metoclopramide in the oral tablet form is used for symptomatic treatment of both acute and recurrent diabetic gastroparesis, in addition to the treatment of gastroesophageal reflux disease (GERD) in patients who have failed to respond to traditional therapy.18 A nasal spray formulation is also indicated to treat adults with acute, recurrent diabetic gastroparesis.21

In the intravenous injection form, it is indicated for the above conditions as well as for the prevention of vomiting that may follow emetogenic chemotherapy or nausea and vomiting after surgery. Intravenous metoclopramide facilitates intubation of the small bowel and stimulates gastric emptying and barium flow in patients who require radiological examination of the stomach or small intestine. In some cases, the delay of gastrointestinal emptying interferes with the radiographic visualization of the gastrointestinal tract, and metoclopramide is used to facilitate emptying in these cases, allowing for adequate diagnostic visualization.19

Some off-label uses of metoclopramide include the management of radiation-induced nausea and vomiting, gastric bezoars, intractable hiccups, and migraine pain.8,9,10,11

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions.17,18,19

Because of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks.4,18

Mechanism of action

Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain.2,17 Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors.2,17,18

TargetActionsOrganism
ADopamine D2 receptor
antagonist
Humans
AMuscarinic acetylcholine receptor M1
agonist
Humans
A5-hydroxytryptamine receptor 4
agonist
Humans
A5-hydroxytryptamine receptor 3A
antagonist
Humans
Absorption

Metoclopramide is rapidly absorbed in the gastrointestinal tract with an absorption rate of about 84%.4 The bioavailability of the oral preparation is reported to be about 40.7%, but can range from 30-100%.2,7

Nasal metoclopramide is 47% bioavailable.21 A 15mg dose reaches a Cmax of 41.0 ng/mL, with a Tmax of 1.25 h, and an AUC of 367 ng*h/mL.21

Volume of distribution

The volume of distribution of metoclopramide is approximately 3.5 L/kg. This implies a high level of tissue distribution. Metoclopramide crosses the placental barrier and can cause extrapyramidal symptoms in the fetus.13,18

Protein binding

Metoclopramide is 30% bound to plasma proteins, mainly to alpha-1-acid glycoprotein.12,19

Metabolism

Metoclopramide undergoes first-pass metabolism and its metabolism varies according to the individual. This drug is metabolized by cytochrome P450 enzymes in the liver.2 CYP2D6 and CYP3A4 both contribute to its metabolism, with CYP2D6 being more heavily involved. CYP1A2 is also a minor contributing enzyme.16 The process of N-4 sulphate conjugation is a primary metabolic pathway of metoclopramide.4

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Route of elimination

About 85% of an orally administered dose was measured in the urine within 72 hours during a pharmacokinetic study. An average of 18% to 22% of 10-20 mg dose was recovered as free drug within 3 days of administration.18

Half-life

The mean elimination half-life of metoclopramide in people with healthy renal function ranges from 5 to 6 hours but is prolonged in patients with renal impairment. Downward dose adjustment should be considered.4,13,18

Clearance

The renal clearance of metoclopramide is 0.16 L/h/kg with a total clearance of 0.7 L/h/kg. Clinical studies showed that the clearance of metoclopramide may be reduced by up to 50% in patients with renal impairment.4 After high intravenous doses, total metoclopramide clearance ranged from 0.31 to 0.69 L/kg/h.14

Adverse Effects
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Toxicity

The rat oral LD50 of metoclopramide is 750 mg/kg.20

Some symptoms of an overdose with metoclopramide include drowsiness, disorientation, and extrapyramidal reactions. Drugs that manage Parkinson's disease or anticholinergic drugs or antihistamines with anticholinergic properties 15 should be employed to treat extrapyramidal symptoms. Normally, these symptoms subside within 24 hours.18 Unintentional overdose in infants receiving the oral solution of metoclopramide resulted in seizures, extrapyramidal symptoms, in addition to a lethargic state.

In addition, methemoglobinemia has been found to occur in premature and full-term neonates after a metoclopramide overdose. Intravenous methylene blue may treat metoclopramide-associated methemoglobinemia. It is important to note that methylene blue administration may lead to hemolytic anemia in patients who suffer from G6PD deficiency, which can result in fatality. Dialysis has not been shown to be effective in sufficiently eliminating metoclopramide in an overdose situation due to low plasma distribution of this drug.18

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Potassium voltage-gated channel subfamily H member 2---(C;C) / (A;C)A > CEffect Directly StudiedThe presence of this polymorphism in KCNH2 may be associated with increased clinical efficacy with metoclopramide.Details
Alpha-1D adrenergic receptor---(T;T) / (A;T)A > TEffect Directly StudiedThe presence of this polymorphism in ADRA1D may be associated with increased clinical efficacy with metoclopramide.Details
Cytochrome P450 2D6CYP2D6*2A(G;G) / (C;G)C > GADR Directly StudiedPatients with this genotype have reduced metabolism of metoclopramide and may be at a higher risk of experiencing adverse events.Details
Cytochrome P450 2D6CYP2D6*2(A;A) / (A;G)G > AADR Directly StudiedPatients with this genotype have reduced metabolism of metoclopramide and may be at a higher risk of experiencing adverse events.Details
Cytochrome P450 2D6CYP2D6*4(A;A) / (A;G)G > ADirectly Studied EffectPatients with this genotype have reduced metabolism of metoclopramide.Details
Potassium voltage-gated channel subfamily H member 2---(T;T) / (C;T)G > AADR Directly StudiedThe presence of this polymorphism in KCNH2 is associated with higher incidences of adverse events from metoclopramide treatment.Details
Multidrug resistance protein 1---(T;T) / (G;T) / (C;T)T Allele / G > T  … show all Effect Directly StudiedPatients with this polymorphism in ABCB1 may have a reduced response to clomipramine.Details
NADH-cytochrome b5 reductase 3---Not AvailableExon 2 c.129C>A / Exon 2 c.149G>A  … show all ADR InferredRisk of methemglobinemia.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Metoclopramide which could result in a higher serum level.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Metoclopramide.
AbametapirThe serum concentration of Metoclopramide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Metoclopramide can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Metoclopramide can be increased when it is combined with Abiraterone.
AcarboseAcarbose may decrease the excretion rate of Metoclopramide which could result in a higher serum level.
AcebutololThe metabolism of Metoclopramide can be decreased when combined with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Metoclopramide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Metoclopramide which could result in a higher serum level.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Metoclopramide.
Additional Data Available
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  • Severity
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Food Interactions
  • Avoid alcohol.
  • Take before a meal. Co-administration with food decreases bioavailability - take 30 minutes before meals.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Metoclopramide hydrochlorideW1792A2RVD54143-57-6KJBLQGHJOCAOJP-UHFFFAOYSA-N
Metoclopramide hydrochloride anhydrous7B1QZY5SWZ7232-21-5RVFUNJWWXKCWNS-UHFFFAOYSA-N
Product Images
International/Other Brands
Cerucal / Degan / Elieten / Maxeran / Maxolon / METOZOLV / Plasil1 / Plazilin / Pramin / Primperan / Pulin / Pylomid / Reliveran
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GimotiSpray15 mg/0.07mLNasalEvoke Pharma, Inc.2020-06-19Not applicableUS flag
Maxeran 5mg TabTablet5 mgOralLabs Nordic Laboratories Inc. Subsidary Of M.M.D.C.1984-12-311998-08-12Canada flag
Maxeran LiqLiquid1 mgOralHoechst Marion Roussel1995-12-312000-07-28Canada flag
Maxeran-10 (10mg Tablet)Tablet10 mgOralHoechst Marion Roussel1995-12-312000-07-28Canada flag
Maxeran-5 (5mg Tablet)Tablet5 mgOralHoechst Marion Roussel1996-10-232000-07-28Canada flag
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousBaxter Laboratories2010-12-092013-04-30US flag
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousHospira, Inc.2008-05-142008-05-14US flag
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousGeneral Injectables & Vaccines2010-08-012017-01-17US flag
MetoclopramideTablet5 mg/1OralVintage Pharmaceuticals, LLC2007-09-132007-09-13US flag
MetoclopramideSolution5 mg/5mLOralANI Pharmaceuticals Inc.2008-10-022008-10-02US flag
Additional Data Available
  • Application Number
    Application Number
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    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-metoclop Tab 10mgTablet10 mgOralApotex Corporation1989-12-31Not applicableCanada flag
Apo-metoclop Tab 5mgTablet5 mgOralApotex Corporation1989-12-31Not applicableCanada flag
MetoclopramideTablet10 mg/1OralTeva Pharmaceuticals USA, Inc.1990-09-30Not applicableUS flag0093 220320180814 13942 19b27lu
MetoclopramideTablet10 mg/1OralAmerincan Health Packaging2013-07-232017-07-31US flag
MetoclopramideTablet5 mg/1OralProficient Rx LP1990-09-30Not applicableUS flag
MetoclopramideInjection, solution5 mg/1mLIntramuscular; IntravenousHospira, Inc.1996-08-022009-09-01US flag
MetoclopramideTablet5 mg/1OralNucare Pharmaceuticals, Inc.1993-07-01Not applicableUS flag
MetoclopramideTablet5 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
MetoclopramideTablet5 mg/1OralPar Pharmaceutical2006-08-282012-03-19US flag
MetoclopramideTablet10 mg/1OralNucare Pharmaceuticals,inc.1990-09-30Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
PCP 100 KitMetoclopramide hydrochloride (10 mg/1) + Bisacodyl (5 mg/1) + Magnesium citrate (1.745 g/29.6mL) + Petrolatum (0.76 g/1g) + Polyethylene glycol (17 g/17g)KitOralAsclemed Usa, Inc.2014-01-02Not applicableUS flag

Categories

ATC Codes
A03FA01 — Metoclopramide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminophenyl ethers. These are aromatic compounds that contain a phenol ether, which carries an amine group on the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Aminophenyl ethers
Direct Parent
Aminophenyl ethers
Alternative Parents
Methoxyanilines / Phenoxy compounds / Methoxybenzenes / Anisoles / Chlorobenzenes / Alkyl aryl ethers / Aryl chlorides / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids
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Substituents
Alkyl aryl ether / Amine / Aminophenyl ether / Aniline or substituted anilines / Anisole / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Carboximidic acid / Carboximidic acid derivative
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Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, substituted aniline, benzamides, monochlorobenzenes (CHEBI:107736)

Chemical Identifiers

UNII
L4YEB44I46
CAS number
364-62-5
InChI Key
TTWJBBZEZQICBI-UHFFFAOYSA-N
InChI
InChI=1S/C14H22ClN3O2/c1-4-18(5-2)7-6-17-14(19)10-8-11(15)12(16)9-13(10)20-3/h8-9H,4-7,16H2,1-3H3,(H,17,19)
IUPAC Name
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide
SMILES
CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC

References

Synthesis Reference
US3177252
General References
  1. Tonini M, Candura SM, Messori E, Rizzi CA: Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis. Pharmacol Res. 1995 May;31(5):257-60. [PubMed:7479521]
  2. Lee A, Kuo B: Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. [PubMed:21278804]
  3. van der Meer YG, Venhuizen WA, Heyland DK, van Zanten AR: Should we stop prescribing metoclopramide as a prokinetic drug in critically ill patients? Crit Care. 2014 Sep 23;18(5):502. doi: 10.1186/s13054-014-0502-4. [PubMed:25672546]
  4. Bateman DN: Clinical pharmacokinetics of metoclopramide. Clin Pharmacokinet. 1983 Nov-Dec;8(6):523-9. doi: 10.2165/00003088-198308060-00003. [PubMed:6360466]
  5. Avalos DJ, Sarosiek I, Loganathan P, McCallum RW: Diabetic gastroparesis: current challenges and future prospects. Clin Exp Gastroenterol. 2018 Sep 25;11:347-363. doi: 10.2147/CEG.S131650. eCollection 2018. [PubMed:30310300]
  6. Lacy BE, Crowell MD, Mathis C, Bauer D, Heinberg LJ: Gastroparesis: Quality of Life and Health Care Utilization. J Clin Gastroenterol. 2018 Jan;52(1):20-24. doi: 10.1097/MCG.0000000000000728. [PubMed:27775961]
  7. Mahajan HS, Gattani S: In situ gels of Metoclopramide Hydrochloride for intranasal delivery: in vitro evaluation and in vivo pharmacokinetic study in rabbits. Drug Deliv. 2010 Jan;17(1):19-27. doi: 10.3109/10717540903447194. Epub 2009 Dec 3. [PubMed:19958151]
  8. Feyer P, Jahn F, Jordan K: Prophylactic Management of Radiation-Induced Nausea and Vomiting. Biomed Res Int. 2015;2015:893013. doi: 10.1155/2015/893013. Epub 2015 Sep 3. [PubMed:26425557]
  9. Eng K, Kay M: Gastrointestinal bezoars: history and current treatment paradigms. Gastroenterol Hepatol (N Y). 2012 Nov;8(11):776-8. [PubMed:24672418]
  10. Wang T, Wang D: Metoclopramide for patients with intractable hiccups: a multicentre, randomised, controlled pilot study. Intern Med J. 2014 Dec;44(12a):1205-9. doi: 10.1111/imj.12542. [PubMed:25069531]
  11. Najjar M, Hall T, Estupinan B: Metoclopramide for Acute Migraine Treatment in the Emergency Department: An Effective Alternative to Opioids. Cureus. 2017 Apr 20;9(4):e1181. doi: 10.7759/cureus.1181. [PubMed:28533997]
  12. Webb D, Buss DC, Fifield R, Bateman DN, Routledge PA: The plasma protein binding of metoclopramide in health and renal disease. Br J Clin Pharmacol. 1986 Mar;21(3):334-6. doi: 10.1111/j.1365-2125.1986.tb05201.x. [PubMed:3964535]
  13. Ross-Lee LM, Eadie MJ, Hooper WD, Bochner F: Single-dose pharmacokinetics of metoclopramide. Eur J Clin Pharmacol. 1981;20(6):465-71. doi: 10.1007/bf00542101. [PubMed:7286058]
  14. McGovern EM, Grevel J, Bryson SM: Pharmacokinetics of high-dose metoclopramide in cancer patients. Clin Pharmacokinet. 1986 Nov-Dec;11(6):415-24. doi: 10.2165/00003088-198611060-00001. [PubMed:3542335]
  15. Allen JC, Gralla R, Reilly L, Kellick M, Young C: Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy. J Clin Oncol. 1985 Aug;3(8):1136-41. doi: 10.1200/JCO.1985.3.8.1136. [PubMed:4020411]
  16. Camilleri M, Shin A: Lessons from pharmacogenetics and metoclopramide: toward the right dose of the right drug for the right patient. J Clin Gastroenterol. 2012 Jul;46(6):437-9. doi: 10.1097/MCG.0b013e3182549528. [PubMed:22688139]
  17. Sasank Isola; Ninos Adams (2019). Metoclopramide, NIH StatPearls. Stat Pearls Publishing.
  18. Metoclopramide FDA label [Link]
  19. Reglan injection FDA label [Link]
  20. Metoclopramide MSDS [Link]
  21. FDA Approved Drug Products: Gimoti Metoclopramide Nasal Spray [Link]
Human Metabolome Database
HMDB0015363
KEGG Drug
D00726
KEGG Compound
C07868
PubChem Compound
4168
PubChem Substance
46505631
ChemSpider
4024
BindingDB
48320
RxNav
6915
ChEBI
107736
ChEMBL
CHEMBL86
ZINC
ZINC000001530716
Therapeutic Targets Database
DAP000530
PharmGKB
PA450475
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Metoclopramide
AHFS Codes
  • 56:32.00 — Prokinetic Agents
FDA label
Download (90.1 KB)
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailablePill Capsule Endoscopy Completion Rates1
4CompletedPreventionInfants, Premature1
4CompletedPreventionMigraine1
4CompletedPreventionNausea / Satisfaction / Vomiting1
4CompletedPreventionPregnancy1
4CompletedPreventionProlonged First Stage of Labor1
4CompletedSupportive CareNausea / Vomiting1
4CompletedTreatmentAcute Migraine1
4CompletedTreatmentAcute Myocardial Infarction (AMI)1
4CompletedTreatmentBreast Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Alaven Pharmaceutical
  • Almus Pharmaceuticals Usa LLC
  • Amerisource Health Services Corp.
  • Anip Acquisition Co.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Baxter International Inc.
  • Bay Pharma Inc.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • General Injectables and Vaccines Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Ipca Laboratories Ltd.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Neighborcare Repackaging Inc.
  • Neuman Distributors Inc.
  • Northstar Rx LLC
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • Pharmaceutical Association
  • Pharmaceutical Packaging Center
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Piramal Healthcare
  • Pliva Inc.
  • Precision Dose Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Qualitest
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Salix Pharmaceuticals
  • Sandhills Packaging Inc.
  • Sandoz
  • Silarx Pharmaceuticals
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • Viasys Medsystems
  • Vintage Pharmaceuticals Inc.
  • Vistapharm Inc.
  • Watson Pharmaceuticals
  • Wockhardt Ltd.
  • Xactdose Inc.
Dosage Forms
FormRouteStrength
Injection, solutionParenteral10 mg
SuspensionOral83.4 mg
SuspensionOral100 mg
Tablet, coatedOral6 mg
Tablet, film coatedOral
SprayNasal15 mg/0.07mL
SyrupOral5 mg/5mL
LiquidOral1 mg
Capsule, extended releaseOral
SolutionOral1 MG/ML
TabletOral10.54 mg
Capsule, extended releaseOral30 mg
Injection, solution10 mg/2mL
SuspensionOral5 mg/5mL
SolutionOral4 mg
InjectionIntramuscular; Intravenous5 mg/1mL
Injection, solutionIntramuscular; Intravenous10 mg/2mL
Injection, solutionIntramuscular; Intravenous5 mg/1mL
SolutionOral0.9 mg/0.9mL
SolutionOral10 mg/10mL
SolutionOral5 mg/5mL
TabletOral10 mg/1
TabletOral5 mg/1
InjectionIntramuscular; Intravenous6.2 MG
Injection, solutionIntravenous5 mg/1mL
PowderNot applicable1 g/1g
Tablet, orally disintegratingOral10 mg/1
Tablet, orally disintegratingOral5 mg/1
LiquidIntramuscular; Intravenous5 mg
LiquidIntravenous5 mg
Injection, solutionParenteral10 MG/2ML
SolutionOral5 mg
TabletOral10 mg
TabletOral5 mg
InjectionIntramuscular; Intravenous10 mg/2ml
Injection, solutionIntravenous10 mg/2ml
Tablet, film coatedOral100 mg
Tablet, film coatedOral20 mg
Tablet, film coatedOral50 mg
KitOral
Solution / dropsOral4 MG/ML
SyrupOral10 MG/10ML
Tablet, coatedOral35000 U FIP
SolutionOral
TabletOral
SyrupOral
SolutionIntramuscular; Intravenous10 mg
SuspensionOral4.5 g
SolutionOral0.09 g
Injection, solutionIntramuscular; Intravenous5.0 mg/1.0mL
SyrupOral1 mg
Capsule, liquid filledOral10 mg
SolutionIntramuscular; Intravenous10 mg/2ml
Solution / drops; suspension / drops
Solution / dropsOral5 mg/5mL
InjectionIntramuscular; Intravenous5 mg/ml
Prices
Unit descriptionCostUnit
Metoclopramide hcl powder7.65USD g
Reglan 10 mg tablet1.81USD tablet
Reglan 5 mg tablet1.41USD tablet
Metoclopramide Hydrochloride 5 mg/ml1.39USD ml
Reglan 5 mg/ml vial0.56USD ml
Metoclopramide HCl 5 mg tablet0.43USD tablet
Metoclopramide 5 mg tablet0.33USD tablet
Metoclopramide 10 mg tablet0.28USD tablet
Metoclopramide 5 mg/ml ampul0.28USD ml
Metoclopramide HCl 10 mg tablet0.27USD tablet
Metoclopramide HCl 5 mg/5ml Solution0.06USD ml
Apo-Metoclop 10 mg Tablet0.06USD tablet
Apo-Metoclop 5 mg Tablet0.06USD tablet
Nu-Metoclopramide 10 mg Tablet0.06USD tablet
Nu-Metoclopramide 5 mg Tablet0.06USD tablet
Pms-Metoclopramide 10 mg Tablet0.06USD tablet
Pms-Metoclopramide 5 mg Tablet0.06USD tablet
Pms-Metoclopramide 1 mg/ml Liquid0.04USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6221392No2001-04-242018-04-09US flag
US6024981No2000-02-152018-04-09US flag
US6413549No2002-07-022017-07-11US flag
US8334281No2010-05-162030-05-16US flag
US6770262No2001-03-292021-03-29US flag
Additional Data Available
  • Filed On
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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)171-173https://www.chemicalbook.com/ChemicalProductProperty_US_CB4236007.aspx
boiling point (°C)418.7https://www.lookchem.com/Metoclopramide-hydrochloride/
logP2.667https://onlinelibrary.wiley.com/doi/full/10.1002/jps.21276
logS-3.18ADME Research, USCD
pKa9.27 https://pubchem.ncbi.nlm.nih.gov/compound/Metoclopramide
Predicted Properties
PropertyValueSource
Water Solubility0.31 mg/mLALOGPS
logP2.18ALOGPS
logP1.4ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)14.49ChemAxon
pKa (Strongest Basic)9.04ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.59 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity83.52 m3·mol-1ChemAxon
Polarizability32.7 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.979
Blood Brain Barrier+0.9713
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7687
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8783
Renal organic cation transporterNon-inhibitor0.7276
CYP450 2C9 substrateNon-substrate0.8602
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6375
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9099
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6223
Ames testNon AMES toxic0.5378
CarcinogenicityNon-carcinogens0.6142
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6332 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8367
hERG inhibition (predictor II)Inhibitor0.8579
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-10fdf9db1550886fc034
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-fcc278321866ecdee26f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0193000000-c044c04d9d51d66ba5a9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0290000000-45d3c52d766c4cd8ae93
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-003r-0970000000-2f2d709cad2c27f798e5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0920000000-ccce0f42f04edf0ecfb3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00lr-0900000000-93aec7dddb8a098f7483
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-e7b25ddf867c24be5347
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0093000000-dc0ce524de60c6a189a7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0290000000-2bca02d9f4cee5acca4e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-003r-0970000000-50fe530dffb9aa59d433
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0920000000-0bb9973fdbe0820dc3d1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00lr-0900000000-4cc6fae9bec9d4c40dbb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-1c4a27b221c7a053d2c3
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fb9-0595000000-db3b50f051cfcc835a69

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. See RE, Lynch AM, Sorg BA: Subchronic administration of clozapine, but not haloperidol or metoclopramide, decreases dopamine D2 receptor messenger RNA levels in the nucleus accumbens and caudate-putamen in rats. Neuroscience. 1996 May;72(1):99-104. [PubMed:8730709]
  2. Harrold MW, Sriburi A, Matsumoto K, Miller DD, Farooqui T, Uretsky N: The interaction of ammonium, sulfonium, and sulfide analogues of metoclopramide with the dopamine D2 receptor. J Med Chem. 1993 Oct 15;36(21):3166-70. [PubMed:8230103]
  3. Kishibayashi N, Karasawa A: Stimulating effects of KW-5092, a novel gastroprokinetic agent, on the gastric emptying, small intestinal propulsion and colonic propulsion in rats. Jpn J Pharmacol. 1995 Jan;67(1):45-50. [PubMed:7745844]
  4. Chemnitius JM, Haselmeyer KH, Gonska BD, Kreuzer H, Zech R: Indirect parasympathomimetic activity of metoclopramide: reversible inhibition of cholinesterases from human central nervous system and blood. Pharmacol Res. 1996 Jul-Aug;34(1-2):65-72. [PubMed:8981558]
  5. Dahlof CG, Hargreaves RJ: Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies? Cephalalgia. 1998 Nov;18(9):593-604. [PubMed:9876882]
  6. Hammer D: Gastroesophageal reflux and prokinetic agents. Neonatal Netw. 2005 Mar-Apr;24(2):51-8; quiz 59-62. [PubMed:15835479]
  7. Bartolini A, Di Cesare Mannelli L, Ghelardini C: Analgesic and antineuropathic drugs acting through central cholinergic mechanisms. Recent Pat CNS Drug Discov. 2011 May 1;6(2):119-40. [PubMed:21585331]
  8. Sasank Isola; Ninos Adams (2019). Metoclopramide, NIH StatPearls. Stat Pearls Publishing.
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Lee A, Kuo B: Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. [PubMed:21278804]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR4
Uniprot ID
Q13639
Uniprot Name
5-hydroxytryptamine receptor 4
Molecular Weight
43760.975 Da
References
  1. Guillemot J, Compagnon P, Cartier D, Thouennon E, Bastard C, Lihrmann I, Pichon P, Thuillez C, Plouin PF, Bertherat J, Anouar Y, Kuhn JM, Yon L, Lefebvre H: Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors. Endocr Relat Cancer. 2009 Mar;16(1):281-90. doi: 10.1677/ERC-08-0190. Epub 2008 Oct 23. [PubMed:18948374]
  2. Lee A, Kuo B: Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. [PubMed:21278804]
  3. Bartolini A, Di Cesare Mannelli L, Ghelardini C: Analgesic and antineuropathic drugs acting through central cholinergic mechanisms. Recent Pat CNS Drug Discov. 2011 May 1;6(2):119-40. [PubMed:21585331]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated potassium channel activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Costall B, Gunning SJ, Naylor RJ, Tyers MB: The effect of GR38032F, novel 5-HT3-receptor antagonist on gastric emptying in the guinea-pig. Br J Pharmacol. 1987 Jun;91(2):263-4. [PubMed:2955843]
  2. Lee A, Kuo B: Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. [PubMed:21278804]
  3. Sasank Isola; Ninos Adams (2019). Metoclopramide, NIH StatPearls. Stat Pearls Publishing.

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Livezey MR, Briggs ED, Bolles AK, Nagy LD, Fujiwara R, Furge LL: Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. Xenobiotica. 2014 Apr;44(4):309-319. doi: 10.3109/00498254.2013.835885. Epub 2013 Sep 6. [PubMed:24010633]
  2. Desta Z, Wu GM, Morocho AM, Flockhart DA: The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6. Drug Metab Dispos. 2002 Mar;30(3):336-43. doi: 10.1124/dmd.30.3.336. [PubMed:11854155]
  3. Camilleri M, Shin A: Lessons from pharmacogenetics and metoclopramide: toward the right dose of the right drug for the right patient. J Clin Gastroenterol. 2012 Jul;46(6):437-9. doi: 10.1097/MCG.0b013e3182549528. [PubMed:22688139]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Lee A, Kuo B: Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. [PubMed:21278804]
  2. Livezey MR, Briggs ED, Bolles AK, Nagy LD, Fujiwara R, Furge LL: Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. Xenobiotica. 2014 Apr;44(4):309-319. doi: 10.3109/00498254.2013.835885. Epub 2013 Sep 6. [PubMed:24010633]
  3. Bailey DG, Dresser G, Arnold JM: Grapefruit-medication interactions: forbidden fruit or avoidable consequences? CMAJ. 2013 Mar 5;185(4):309-16. doi: 10.1503/cmaj.120951. Epub 2012 Nov 26. [PubMed:23184849]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Lee A, Kuo B: Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5(5):653-662. [PubMed:21278804]
  2. Livezey MR, Briggs ED, Bolles AK, Nagy LD, Fujiwara R, Furge LL: Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. Xenobiotica. 2014 Apr;44(4):309-319. doi: 10.3109/00498254.2013.835885. Epub 2013 Sep 6. [PubMed:24010633]
  3. Camilleri M, Shin A: Lessons from pharmacogenetics and metoclopramide: toward the right dose of the right drug for the right patient. J Clin Gastroenterol. 2012 Jul;46(6):437-9. doi: 10.1097/MCG.0b013e3182549528. [PubMed:22688139]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Webb D, Buss DC, Fifield R, Bateman DN, Routledge PA: The plasma protein binding of metoclopramide in health and renal disease. Br J Clin Pharmacol. 1986 Mar;21(3):334-6. doi: 10.1111/j.1365-2125.1986.tb05201.x. [PubMed:3964535]
  2. Reglan injection FDA label [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Pottier G, Marie S, Goutal S, Auvity S, Peyronneau MA, Stute S, Boisgard R, Dolle F, Buvat I, Caille F, Tournier N: Imaging the Impact of the P-Glycoprotein (ABCB1) Function on the Brain Kinetics of Metoclopramide. J Nucl Med. 2016 Feb;57(2):309-14. doi: 10.2967/jnumed.115.164350. Epub 2015 Nov 19. [PubMed:26585058]
  2. Caille F, Goutal S, Marie S, Auvity S, Cisternino S, Kuhnast B, Pottier G, Tournier N: Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide. Contrast Media Mol Imaging. 2018 May 8;2018:7310146. doi: 10.1155/2018/7310146. eCollection 2018. [PubMed:29853808]
  3. Bauer M, Tournier N, Langer O: Imaging P-Glycoprotein Function at the Blood-Brain Barrier as a Determinant of the Variability in Response to Central Nervous System Drugs. Clin Pharmacol Ther. 2019 May;105(5):1061-1064. doi: 10.1002/cpt.1402. Epub 2019 Mar 23. [PubMed:30903694]

Drug created on June 13, 2005 07:24 / Updated on October 29, 2020 19:26

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