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Identification
NameDomperidone
Accession NumberDB01184  (APRD00418)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1-(3-(4-(5-chloro-2-oxo-2,3-Dihydrobenzo[D]imidazol-1-yl)piperidin-1-yl)propyl)-1H-benzo[D]imidazol-2(3H)-oneNot AvailableNot Available
5-chloro-1-(1-(3-(2-oxo-1-Benzimidazolinyl)propyl)-4-piperidyl)-2-benzimidazolinoneNot AvailableNot Available
5-chloro-1-(1-(3-(2-oxo-2,3-Dihydrobenzo[D]imidazol-1-yl)propyl)piperidin-4-yl)-1H-benzo[D]imidazol-2(3H)-oneNot AvailableNot Available
5-chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-oneNot AvailableNot Available
DomperidonaNot AvailableNot Available
DomperidonumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
EucitonRoux-Ocefa
MoperidonaSidus
MotiliumJanssen
NauzelinKyowa Hakko Kirin
Brand mixturesNot Available
CategoriesNot Available
CAS number57808-66-9
WeightAverage: 425.911
Monoisotopic: 425.161852744
Chemical FormulaC22H24ClN5O2
InChI KeyFGXWKSZFVQUSTL-UHFFFAOYSA-N
InChI
InChI=1S/C22H24ClN5O2/c23-15-6-7-20-18(14-15)25-22(30)28(20)16-8-12-26(13-9-16)10-3-11-27-19-5-2-1-4-17(19)24-21(27)29/h1-2,4-7,14,16H,3,8-13H2,(H,24,29)(H,25,30)
IUPAC Name
5-chloro-1-{1-[3-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)propyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one
SMILES
ClC1=CC2=C(C=C1)N(C1CCN(CCCN3C(=O)NC4=CC=CC=C34)CC1)C(=O)N2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzimidazoles
SubclassNot Available
Direct parentBenzimidazoles
Alternative parentsAminopiperidines; Chlorobenzenes; N-substituted Imidazoles; Aryl Chlorides; Tertiary Amines; Polyamines; Organochlorides
Substituents4-aminopiperidine; chlorobenzene; aryl chloride; benzene; aryl halide; n-substituted imidazole; piperidine; azole; imidazole; tertiary amine; polyamine; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Pharmacology
IndicationFor management of dyspepsia, heartburn, epigastric pain, nausea, and vomiting.
PharmacodynamicsDomperidone is a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.
Mechanism of actionDomperidone acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant. The gastroprokinetic properties of domperidone are related to its peripheral dopamine receptor blocking properties. Domperidone facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure. Antiemetic: The antiemetic properties of domperidone are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level. It has strong affinities for the D2 and D3 dopamine receptors, which are found in the chemoreceptor trigger zone, located just outside the blood brain barrier, which - among others - regulates nausea and vomiting
AbsorptionFast
Volume of distributionNot Available
Protein binding91%-93%
Metabolism
SubstrateEnzymesProduct
Domperidone
5-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneDetails
Route of eliminationNot Available
Half life7 hours
ClearanceNot Available
ToxicitySide effects include galactorrhea, gynecomastia, or menstrual irregularities.
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 + 0.9967
Blood Brain Barrier + 0.8686
Caco-2 permeable - 0.8957
P-glycoprotein substrate Substrate 0.7029
P-glycoprotein inhibitor I Inhibitor 0.7244
P-glycoprotein inhibitor II Inhibitor 0.628
Renal organic cation transporter Inhibitor 0.6546
CYP450 2C9 substrate Non-substrate 0.7974
CYP450 2D6 substrate Non-substrate 0.9117
CYP450 3A4 substrate Substrate 0.6392
CYP450 1A2 substrate Inhibitor 0.8737
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8933
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Inhibitor 0.5577
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8695
Ames test Non AMES toxic 0.6608
Carcinogenicity Non-carcinogens 0.922
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 1.9828 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.7527
hERG inhibition (predictor II) Inhibitor 0.917
Pharmacoeconomics
ManufacturersNot Available
Packagers
  • Professional Co.
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Domperidone bp powder55.2USDg
Ratio-Domperidone Maleate 10 mg Tablet0.16USDtablet
Apo-Domperidone 10 mg Tablet0.16USDtablet
Mylan-Domperidone 10 mg Tablet0.16USDtablet
Novo-Domperidone 10 mg Tablet0.16USDtablet
Nu-Domperidone 10 mg Tablet0.16USDtablet
Pms-Domperidone 10 mg Tablet0.15USDtablet
Ran-Domperidone 10 mg Tablet0.15USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point242.5 °CVanderberk, J., Kennis, L.E.J., Van der Aa, M.J.M.C. and Van Heertum, A.H.M.T.; U.S. Patents 4,066,772; January 3,1978; 4.1 10,333; August 29,1978; 4,126,687; November 21, 1978; 4,126,688; November 21,1978; 4,160,836; July 10,1979 and 4,175,129; November 20,1979; all assigned to Janssen Pharmaceutica NV (Belgium).
water solubility0.986 mg/LNot Available
logP3.90EL TAYER,N ET AL. (1985)
pKa7.9EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.0925ALOGPS
logP3.7ALOGPS
logP2.9ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)12.52ChemAxon
pKa (Strongest Basic)7.03ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.92 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity119.37 m3·mol-1ChemAxon
Polarizability45.61 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Vanderberk, J., Kennis, L.E.J., Van der Aa, M.J.M.C. and Van Heertum, A.H.M.T.; U.S. Patents 4,066,772; January 3,1978; 4.1 10,333; August 29,1978; 4,126,687; November 21, 1978; 4,126,688; November 21,1978; 4,160,836; July 10,1979 and 4,175,129; November 20,1979; all assigned to Janssen Pharmaceutica NV (Belgium).

General Reference
  1. Silvers D, Kipnes M, Broadstone V, Patterson D, Quigley EM, McCallum R, Leidy NK, Farup C, Liu Y, Joslyn A: Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM-USA-5 Study Group. Clin Ther. 1998 May-Jun;20(3):438-53. Pubmed
External Links
ResourceLink
KEGG DrugD01745
PubChem Compound3151
PubChem Substance46508314
ChemSpider3039
BindingDB50241107
ChEBI31515
ChEMBLCHEMBL219916
Therapeutic Targets DatabaseDAP001368
PharmGKBPA134711056
IUPHAR965
Guide to Pharmacology965
Drug Product Database2238444
WikipediaDomperidone
ATC CodesA03FA03
AHFS Codes
  • 56:32.00
  • 56:92.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.8 KB)
Interactions
Drug Interactions
Drug
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Take 15 to 30 minutes before meals.

Targets

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. Cavallotti C, Nuti F, Bruzzone P, Mancone M: Age-related changes in dopamine D2 receptors in rat heart and coronary vessels. Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):412-8. Pubmed
  2. Osinski MA, Uchic ME, Seifert T, Shaughnessy TK, Miller LN, Nakane M, Cox BF, Brioni JD, Moreland RB: Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets. Pharmacol Biochem Behav. 2005 May;81(1):211-9. Pubmed
  3. de Mey C, Enterling D, Meineke I, Yeulet S: Interactions between domperidone and ropinirole, a novel dopamine D2-receptor agonist. Br J Clin Pharmacol. 1991 Oct;32(4):483-8. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. Ali I, Gupta VK, Singh P, Pant HV: Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31. Epub 2005 Jul 22. Pubmed

2. D(3) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(3) dopamine receptor P35462 Details

References:

  1. Freedman SB, Patel S, Marwood R, Emms F, Seabrook GR, Knowles MR, McAllister G: Expression and pharmacological characterization of the human D3 dopamine receptor. J Pharmacol Exp Ther. 1994 Jan;268(1):417-26. Pubmed

Enzymes

1. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

2. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Chang SY, Fancher RM, Zhang H, Gan J: Mechanism-based inhibition of human cytochrome P4503A4 by domperidone. Xenobiotica. 2010 Feb;40(2):138-45. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Simard C, Michaud V, Gibbs B, Masse R, Lessard E, Turgeon J: Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone. Xenobiotica. 2004 Nov-Dec;34(11-12):1013-23. Pubmed

4. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 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

5. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 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

6. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 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

7. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed
  2. Schinkel AH, Wagenaar E, Mol CA, van Deemter L: P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest. 1996 Jun 1;97(11):2517-24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 15, 2014 14:42