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Identification
NameMetoclopramide
Accession NumberDB01233  (APRD00665)
Typesmall molecule
Groupsapproved, investigational
Description

A dopamine D2 antagonist that is used as an antiemetic. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-methoxy-5-chloroprocainamideNot AvailableNot Available
MetoclopramidaSpanishINN
MetoclopramidumLatinINN
Salts
Name/CAS Structure Properties
Metoclopramide Hydrochloride
Thumb
  • InChI Key: KJBLQGHJOCAOJP-UHFFFAOYSA-N
  • Monoisotopic Mass: 353.127297095
  • Average Mass: 354.273
DBSALT000393
Brand names
NameCompany
CerucalNot Available
DeganNot Available
ElietenNot Available
MaxeranNot Available
MaxolonNot Available
Plasil1Not Available
PlazilinNot Available
PraminNot Available
PrimperanNot Available
PulinNot Available
PylomidNot Available
ReglanNot Available
ReliveranNot Available
Brand mixturesNot Available
Categories
CAS number364-62-5
WeightAverage: 299.796
Monoisotopic: 299.14005467
Chemical FormulaC14H22ClN3O2
InChI KeyInChIKey=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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzoic Acid and Derivatives
Direct parentSalicylamides
Alternative parentsAminobenzamides; Benzoyl Derivatives; Anisoles; Anilines; Alkyl Aryl Ethers; Chlorobenzenes; Aryl Chlorides; Primary Aromatic Amines; Tertiary Amines; Secondary Carboxylic Acid Amides; Polyamines; Enolates; Carboxylic Acids; Organochlorides
Substituentsbenzoyl; phenol ether; anisole; alkyl aryl ether; aniline; chlorobenzene; aryl chloride; aryl halide; primary aromatic amine; carboxamide group; secondary carboxylic acid amide; tertiary amine; ether; polyamine; carboxylic acid; carboxylic acid derivative; enolate; organochloride; organohalogen; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the salicylamides. These are carboxamide derivatives of salicylic acid.
Pharmacology
IndicationFor the treatment of gastroesophageal reflux disease (GERD). It is also used in treating nausea and vomiting, and to increase gastric emptying.
PharmacodynamicsMetoclopramide, although chemically related to procainamide, does not possess local anesthetic or antiarrhythmic properties. Metoclopramide is used to enhance GI motility, to treat diabetic gastroparesis, as an antinauseant, and to facilitate intubation of the small bowel during radiologic examination. Metoclopramide may be used to treat chemotherapy-induced emesis and as a radiosensitizing agents in the treatment of non-small cell lung carcinoma and glioblastomas in the future.
Mechanism of actionMetoclopramide inhibits gastric smooth muscle relaxation produced by dopamine, therefore increasing cholinergic response of the gastrointestinal smooth muscle. It accelerates intestinal transit and gastric emptying by preventing relaxation of gastric body and increasing the phasic activity of antrum. Simultaneously, this action is accompanied by relaxation of the upper small intestine, resulting in an improved coordination between the body and antrum of the stomach and the upper small intestine. Metoclopramide also decreases reflux into the esophagus by increasing the resting pressure of the lower esophageal sphincter and improves acid clearance from the esophagus by increasing amplitude of esophageal peristaltic contractions. Metoclopramide's dopamine antagonist action raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves. Studies have also shown that high doses of metoclopramide can antagonize 5-hydroxytryptamine (5-HT) receptors in the peripheral nervous system in animals.
AbsorptionRapidly and well absorbed (oral bioavailability 80±15.5%).
Volume of distribution
  • 4.4±0.65 L/kg
Protein binding30%
Metabolism

Hepatic

Route of eliminationApproximately 85% of the radioactivity of an orally administered dose appears in the urine within 72 hours.
Half life5-6 hr
Clearance
  • 0.67 +/- 0.14 L/hr/kg [infants (0.9-5.4 months) with gastroesophageal reflux (GER)]
ToxicityOral, mouse LD50: 280 mg/kg. Signs of overdose include drowsiness, disorientation, and extrapyramidal reactions.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.979
Blood Brain Barrier + 0.9713
Caco-2 permeable + 0.8866
P-glycoprotein substrate Substrate 0.7687
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.8783
Renal organic cation transporter Non-inhibitor 0.7276
CYP450 2C9 substrate Non-substrate 0.8602
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.6375
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9099
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6223
Ames test Non AMES toxic 0.5378
Carcinogenicity Non-carcinogens 0.6142
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.6332 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8367
hERG inhibition (predictor II) Inhibitor 0.8579
Pharmacoeconomics
Manufacturers
  • Roxane laboratories inc
  • Abraxis pharmaceutical products
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Norbrook laboratories ltd
  • Smith and nephew solopak div smith and nephew
  • Teva parenteral medicines inc
  • Baxter healthcare corp anesthesia critical care
  • Actavis mid atlantic llc
  • Ani pharmaceuticals inc
  • Morton grove pharmaceuticals inc
  • Paco research corp
  • Pharmaceutical assoc inc div beach products
  • Silarx pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Vistapharm inc
  • Wockhardt eu operations (swiss) ag
  • Ah robins co
  • Salix pharmaceuticals inc
  • Alaven pharmaceutical llc
  • Quantum pharmics ltd
  • King pharmaceuticals inc
  • Actavis elizabeth llc
  • Clonmel healthcare ltd
  • Halsey drug co inc
  • Interpharm inc
  • Ipca laboratories ltd
  • Mutual pharmaceutical co inc
  • Northstar healthcare holdings ltd
  • Par pharmaceutical inc
  • Sandoz inc
  • Schering corp sub schering plough corp
  • Superpharm corp
  • Usl pharma inc
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
LiquidIntramuscular
LiquidIntravenous
LiquidOral
TabletOral
Prices
Unit descriptionCostUnit
Metoclopramide hcl powder7.65USDg
Reglan 10 mg tablet1.81USDtablet
Reglan 5 mg tablet1.41USDtablet
Metoclopramide Hydrochloride 5 mg/ml1.39USDml
Reglan 5 mg/ml vial0.56USDml
Metoclopramide HCl 5 mg tablet0.43USDtablet
Metoclopramide 5 mg tablet0.33USDtablet
Metoclopramide 10 mg tablet0.28USDtablet
Metoclopramide 5 mg/ml ampul0.28USDml
Metoclopramide HCl 10 mg tablet0.27USDtablet
Metoclopramide HCl 5 mg/5ml Solution0.06USDml
Apo-Metoclop 10 mg Tablet0.06USDtablet
Apo-Metoclop 5 mg Tablet0.06USDtablet
Nu-Metoclopramide 10 mg Tablet0.06USDtablet
Nu-Metoclopramide 5 mg Tablet0.06USDtablet
Pms-Metoclopramide 10 mg Tablet0.06USDtablet
Pms-Metoclopramide 5 mg Tablet0.06USDtablet
Pms-Metoclopramide 1 mg/ml Liquid0.04USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States60249811998-04-092018-04-09
United States64135491997-07-112017-07-11
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point147.25 °CPhysProp
water solubility200 mg/L (at 25 °C)MERCK (1989)
logP2.62HANSCH,C ET AL. (1995)
logS-3.18ADME Research, USCD
pKa9.27 (at 25 °C)EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
water solubility3.10e-01 g/lALOGPS
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 area67.59ChemAxon
rotatable bond count7ChemAxon
refractivity83.52ChemAxon
polarizability32.7ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3177252
General Reference
  1. JUSTIN-BESANCON L, LAVILLE C: [ANTIEMETIC ACTION OF METOCLOPRAMIDE WITH RESPECT TO APOMORPHINE AND HYDERGINE.] C R Seances Soc Biol Fil. 1964;158:723-7. Pubmed
  2. 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
External Links
ResourceLink
KEGG DrugD00726
KEGG CompoundC07868
PubChem Compound4168
PubChem Substance46505631
ChemSpider4024
BindingDB50000491
ChEBI107736
ChEMBLCHEMBL86
Therapeutic Targets DatabaseDAP000530
PharmGKBPA450475
IUPHAR241
Guide to Pharmacology241
Drug Product Database2243563
RxListhttp://www.rxlist.com/cgi/generic2/metoclo.htm
Drugs.comhttp://www.drugs.com/metoclopramide.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/reg1369.shtml
WikipediaMetoclopramide
ATC CodesA03FA01
AHFS Codes
  • 56:32.00
PDB EntriesNot Available
FDA labelshow(90.1 KB)
MSDSshow(73.2 KB)
Interactions
Drug Interactions
Drug
CyclosporineMetoclopramide increases serum levels of cyclosporine
L-DOPALevodopa decreases the effect of metoclopramide
LurasidoneIncreases toxicity and risk of extrapyramidal effects of lurasidone by antidopaminergic effects. Concomitant therapy should be avoided.
PaliperidoneMetoclopramide may increase the risk of extrapyramidal side effects of paliperidone. Concomitant therapy should be avoided.
TacrolimusMetoclopramide may increase the concentration of Tacrolimus in the blood. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Metoclopramide therapy is initiated, discontinued or altered.
TetrabenazineSimilar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
VenlafaxinePossible serotoninergic syndrome with this combination
VilazodoneSeek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome.
ZuclopenthixolAdditive dopamine D2 receptor antagonism may cause dopaminergic imbalance in the nigrostriatal (dopamine D1 receptors) and striatopallidal (dopamine D2 receptors). Increased risk of extrapyramidal reactions and neuroleptic malignant syndrome. Concomitant therapy should be avoided.
Zuclopenthixol acetateAdditive dopamine D2 receptor antagonism may cause dopaminergic imbalance in the nigrostriatal (dopamine D1 receptors) and striatopallidal (dopamine D2 receptors). Increased risk of extrapyramidal reactions and neuroleptic malignant syndrome. Concomitant therapy should be avoided.
Zuclopenthixol decanoateAdditive dopamine D2 receptor antagonism may cause dopaminergic imbalance in the nigrostriatal (dopamine D1 receptors) and striatopallidal (dopamine D2 receptors). Increased risk of extrapyramidal reactions and neuroleptic malignant syndrome. Concomitant therapy should be avoided.
Food Interactions
  • Food reduces availability, take 30 minutes before meals. Avoid alcohol.

1. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. Hammer D: Gastroesophageal reflux and prokinetic agents. Neonatal Netw. 2005 Mar-Apr;24(2):51-8; quiz 59-62. Pubmed

2. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Burger DM, Wiestner T, Hubler M, Binder H, Keiser M, Arnold S: Effect of anticholinergics (atropine, glycopyrrolate) and prokinetics (metoclopramide, cisapride) on gastric motility in beagles and labrador retrievers. J Vet Med A Physiol Pathol Clin Med. 2006 Mar;53(2):97-107. Pubmed
  4. Hammer D: Gastroesophageal reflux and prokinetic agents. Neonatal Netw. 2005 Mar-Apr;24(2):51-8; quiz 59-62. Pubmed

3. 5-hydroxytryptamine receptor 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 4 Q13639 Details

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. Epub 2008 Oct 23. Pubmed

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 11B1, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 11B1, mitochondrial P15538 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 11B2, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 11B2, mitochondrial P19099 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Steroid 17-alpha-hydroxylase/17,20 lyase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Steroid 17-alpha-hydroxylase/17,20 lyase P05093 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24