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Identification
Name Metoclopramide
Accession Number DB01233 (APRD00665)
Type small molecule
Groups approved
Description

A dopamine D2 antagonist that is used as an antiemetic. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Metaclopramide
Metaclopromide
Methochlopramide
Methoclopramide
Metochlopramide
Metoclopramida [INN-Spanish]
Metoclopramide Hcl
Metoclopramide Hydrochloride
Metoclopramidum [INN-Latin]
Salts Not Available
Brand names
Name Company
Apo-Metoclop
Cerucal
Clopra
Clopra-Yellow
Clopromate
DEL
Duraclamid
Elieten
Emetid
Emitasol
Emperal
Eucil
Gastrese
Gastro-Timelets
Gastrobid
Gastromax
Gastronerton
Gastrosil
Gastrotablinen
Gastrotem
Imperan
Maxeran
Maxolon
Meclopran
Metamide
Metoclol
Metoclopramide Intensol
Metoclopramide Omega
Metocobil
Metramid
Moriperan
Mygdalon
Neu-Sensamide
Nu-Metoclopramide
Octamide
Parmid
Paspertin
Peraprin
Plasil
Pms-Metoclopramide
Pramidin
Pramiel
Pramin
Primperan
Reclomide
Reglan
Reliveran
Terperan
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Brand mixtures Not Available
Categories
  • Antiemetics
  • Dopamine Antagonists
  • Prokinetic Agents
CAS number 364-62-5
Weight Average: 299.796
Monoisotopic: 299.14005467
Chemical Formula C14H22ClN3O2
InChI Key InChIKey=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)
Plain Text
IUPAC Name
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide
SMILES
CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Benzoyl Derivatives
  • Benzamides
Substructures
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Phenyl Esters
  • Benzamides
  • Anilines
Pharmacology
Indication For the treatment of gastroesophageal reflux disease (GERD). It is also used in treating nausea and vomiting, and to increase gastric emptying.
Pharmacodynamics Metoclopramide, 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 action Metoclopramide 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.
Absorption Rapidly and well absorbed (oral bioavailability 80±15.5%).
Volume of distribution
  • 4.4±0.65 L/kg
Protein binding 30%
Metabolism Hepatic
Route of elimination Approximately 85% of the radioactivity of an orally administered dose appears in the urine within 72 hours.
Half life 5-6 hr
Clearance
  • 0.67 +/- 0.14 L/hr/kg [infants (0.9-5.4 months) with gastroesophageal reflux (GER)]
Toxicity Oral, mouse LD50: 280 mg/kg. Signs of overdose include drowsiness, disorientation, and extrapyramidal reactions.
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Form Route Strength
Liquid Intramuscular
Liquid Intravenous
Liquid Oral
Tablet Oral
Prices
Unit description Cost Unit
Metoclopramide hcl powder 7.65 USD g
Reglan 10 mg tablet 1.81 USD tablet
Reglan 5 mg tablet 1.41 USD tablet
Metoclopramide Hydrochloride 5 mg/ml 1.39 USD ml
Reglan 5 mg/ml vial 0.56 USD ml
Metoclopramide HCl 5 mg tablet 0.43 USD tablet
Metoclopramide 5 mg tablet 0.33 USD tablet
Metoclopramide 10 mg tablet 0.28 USD tablet
Metoclopramide 5 mg/ml ampul 0.28 USD ml
Metoclopramide HCl 10 mg tablet 0.27 USD tablet
Metoclopramide HCl 5 mg/5ml Solution 0.06 USD ml
Apo-Metoclop 10 mg Tablet 0.06 USD tablet
Apo-Metoclop 5 mg Tablet 0.06 USD tablet
Nu-Metoclopramide 10 mg Tablet 0.06 USD tablet
Nu-Metoclopramide 5 mg Tablet 0.06 USD tablet
Pms-Metoclopramide 10 mg Tablet 0.06 USD tablet
Pms-Metoclopramide 5 mg Tablet 0.06 USD tablet
Pms-Metoclopramide 1 mg/ml Liquid 0.04 USD ml
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6024981 1998-04-09 2018-04-09
United States 6413549 1997-07-11 2017-07-11
Properties
State solid
Experimental Properties
Property Value Source
melting point 147.25 °C PhysProp
water solubility 200 mg/L (at 25 °C) MERCK (1989)
logP 2.62 HANSCH,C ET AL. (1995)
logS -3.18 ADME Research, USCD
pKa 9.27 (at 25 °C) EL TAYAR,N ET AL. (1985)
Predicted Properties
Property Value Source
water solubility 3.10e-01 g/l ALOGPS
logP 2.18 ALOGPS
logP 1.4 ChemAxon
logS -3 ALOGPS
pKa (strongest acidic) 14.49 ChemAxon
pKa (strongest basic) 9.04 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 67.59 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 83.52 ChemAxon
polarizability 32.7 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00726 Link_out
KEGG Compound C07868 Link_out
PubChem Compound 4168 Link_out
PubChem Substance 46505631 Link_out
ChemSpider 4024 Link_out
BindingDB 50000491 Link_out
ChEBI 107736 Link_out
ChEMBL 107736 Link_out
Therapeutic Targets Database DAP000530 Link_out
PharmGKB PA450475 Link_out
IUPHAR 241 Link_out
Guide to Pharmacology 241 Link_out
Drug Product Database 2243563 Link_out
RxList http://www.rxlist.com/cgi/generic2/metoclo.htm Link_out
Drugs.com http://www.drugs.com/metoclopramide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/reg1369.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Metoclopramide Link_out
ATC Codes
  • A03FA01
AHFS Codes
  • 56:32.00
PDB Entries Not Available
FDA label show (90.1 KB)
MSDS show (73.2 KB)
Interactions
Drug Interactions
Drug Interaction
Cyclosporine Metoclopramide increases serum levels of cyclosporine
Levodopa Levodopa decreases the effect of metoclopramide
Lurasidone Increases toxicity and risk of extrapyramidal effects of lurasidone by antidopaminergic effects. Concomitant therapy should be avoided.
Paliperidone Metoclopramide may increase the risk of extrapyramidal side effects of paliperidone. Concomitant therapy should be avoided.
Tacrolimus Metoclopramide 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.
Tetrabenazine Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Venlafaxine Possible serotoninergic syndrome with this combination
Vilazodone Seek 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.
Zuclopenthixol Additive 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.
Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 4 receptor

Pharmacological action: unknown
Actions: agonist

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 is mediated by G proteins that stimulate adenylate cyclase

Organism class: human
UniProt ID: Q13639 Link_out
Gene: HTR4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB

UniProt ID: P15538 Link_out
Gene: CYP11B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Preferentially catalyzes the conversion of 11- deoxycorticosterone to aldosterone via corticosterone and 18- hydroxycorticosterone

UniProt ID: P19099 Link_out
Gene: CYP11B2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Cytochrome P450 17A1

Actions: inhibitor

Conversion of pregnenolone and progesterone to their 17- alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty

UniProt ID: P05093 Link_out
Gene: CYP17A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:20