Domperidone

Common Name

Domperidone Description

Domperidone is only found in individuals that have used or taken this drug. It 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. [PubChem]Domperidone acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimliant. 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 – regliates nausea and vomiting Structure

Synonyms

Value Source 1-(3-(4-(5-chloro-2-oxo-2,3-dihydrobenzo[D]Imidazol-1-yl)piperidin-1-yl)propyl)-1H-benzo[D]imidazol-2(3H)-oneChEBI 5-chloro-1-(1-(3-(2-oxo-1-Benzimidazolinyl)propyl)-4-piperidyl)-2-benzimidazolinoneChEBI 5-chloro-1-(1-(3-(2-oxo-2,3-dihydrobenzo[D]Imidazol-1-yl)propyl)piperidin-4-yl)-1H-benzo[D]imidazol-2(3H)-oneChEBI 5-chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-oneChEBI DomperidonaChEBI DomperidonumChEBI Domperidon hexalMeSH Domperidon tevaMeSH Domperidon-tevaMeSH Domperidone monohydrochlorideMeSH GastrocureMeSH Novopharm brand OF domperidone maleateMeSH PMS-DomperidoneMeSH Ratiopharm brand OF domperidone maleateMeSH apo DomperidoneMeSH DomperidonMeSH Domperidon alMeSH Domperidon stadaMeSH Domperidona gamirMeSH Domperidone maleateMeSH Gry brand OF domperidone maleateMeSH MotiliumMeSH NauzelinMeSH Nu-pharm brand OF domperidone maleateMeSH Rottapharm brand OF domperidoneMeSH Stadapharm brand OF domperidone maleateMeSH Taxandria brand OF domperidone maleateMeSH ratio DomperidoneMeSH DomidonMeSH Domperidone maleate (1:1)MeSH Hexal, domperidonMeSH Monohydrochloride, domperidoneMeSH novo DomperidoneMeSH Nu pharm brand OF domperidone maleateMeSH PMS DomperidoneMeSH Pharmascience brand OF domperidone maleateMeSH Pierre fabre brand OF domperidoneMeSH Teva brand OF domperidone maleateMeSH ratio-DomperidoneMeSH Aliud brand OF domperidone maleateMeSH apo-DomperidoneMeSH Apotex brand OF domperidone maleateMeSH Gamir, domperidonaMeSH Hexal brand OF domperidone maleateMeSH Janssen brand OF domperidoneMeSH Maleate, domperidoneMeSH novo-DomperidoneMeSH Nu domperidoneMeSH Nu-domperidoneMeSH PéridysMeSH Stada, domperidonMeSH

Chemical Formlia

C₂₂H₂₄ClN₅O₂ Average Molecliar Weight

425.911 Monoisotopic Molecliar Weight

425.161852744 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 Traditional Name

motilium CAS Registry Number

57808-66-9 SMILES

InChI Identifier

InChI Key

FGXWKSZFVQUSTL-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as 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). Kingdom

Organic compounds Super Class

Organoheterocyclic compounds Class

Benzimidazoles Sub Class

Not Available Direct Parent

Benzimidazoles Alternative Parents

Piperidines

N-substituted imidazoles

Benzenoids

Aryl chlorides

Heteroaromatic compounds

Ureas

Trialkylamines

Azacyclic compounds

Organopnictogen compounds

Organooxygen compounds

Organochlorides

Organic oxides

Hydrocarbon derivatives

Substituents

Benzimidazole

Aryl chloride

Aryl halide

N-substituted imidazole

Piperidine

Benzenoid

Azole

Imidazole

Heteroaromatic compound

Tertiary aliphatic amine

Tertiary amine

Urea

Azacycle

Hydrocarbon derivative

Organooxygen compound

Organonitrogen compound

Organochloride

Organohalogen compound

Organic oxide

Organopnictogen compound

Amine

Organic oxygen compound

Organic nitrogen compound

Aromatic heteropolycyclic compound

Molecliar Framework

Aromatic heteropolycyclic compounds External Descriptors

benzimidazoles (CHEBI:31515 )

heteroarylpiperidine (CHEBI:31515 )

Ontology Status

Expected but not Quantified Origin

Drug

Biofunction

Antiemetics

Dopamine Antagonists

Application

Pharmaceutical

Cellliar locations

Membrane

Physical Properties State

Solid Experimental Properties

Property Value Reference Melting Point242.5 °CNot Available Boiling PointNot AvailableNot Available Water Solubility9.25e-02 g/LNot Available LogP2.4Not Available

Predicted Properties

Property Value Source Water Solubility0.092 mg/mLALOGPS 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 ŲChemAxon Rotatable Bond Count5ChemAxon Refractivity119.37 m³·mol^-1ChemAxon Polarizability45.61 ųChemAxon Number of Rings5ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

Spectra Spectra

Spectrum Type Description Splash Key LC-MS/MS

LC-MS/MS Spectrum – , positivesplash10-004i-0300900000-912de932579a7a2a6e2fView in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-004i-0900300000-877326ac38180c1229cdView in MoNA Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

Biological Properties Cellliar Locations

Membrane

Biofluid Locations

Blood

Urine

Tissue Location

Not Available Pathways

Not Available Normal Concentrations

Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01184

21059682

details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01184

21059682

details

Abnormal Concentrations

Not Available Associated Disorders and Diseases Disease References

None Associated OMIM IDs

None External Links DrugBank ID

DB01184 DrugBank Metabolite ID

Not Available Phenol Explorer Compound ID

Not Available Phenol Explorer Metabolite ID

Not Available FoodDB ID

Not Available KNApSAcK ID

Not Available Chemspider ID

3039 KEGG Compound ID

Not Available BioCyc ID

Not Available BiGG ID

Not Available Wikipedia Link

Domperidone NuGOwiki Link

HMDB15315 Metagene Link

HMDB15315 METLIN ID

Not Available PubChem Compound

3151 PDB ID

Not Available ChEBI ID

31515

Product: Jervine

References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Download (PDF) General References

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:9663360 ]

Enzymes

General function:

Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

Gene Name:

CYP3A4

Uniprot ID:

P08684

Molecular weight:

57255.585

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. doi: 10.3109/00498250903406762. [PubMed:20082577 ]
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
3. 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:15801545 ]

General function:

Involved in monooxygenase 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 antidepressants.

Gene Name:

CYP2D6

Uniprot ID:

P10635

Molecular weight:

55768.94

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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.

Gene Name:

CYP2B6

Uniprot ID:

P20813

Molecular weight:

56277.81

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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP3A5

Uniprot ID:

P20815

Molecular weight:

57108.065

General function:

Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP3A7

Uniprot ID:

P24462

Molecular weight:

57525.03

General function:

Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.

Gene Name:

CYP1A2

Uniprot ID:

P05177

Molecular weight:

58406.915

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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in monooxygenase 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).

Gene Name:

CYP2C8

Uniprot ID:

P10632

Molecular weight:

55824.275

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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

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

Gene Name:

DRD2

Uniprot ID:

P14416

Molecular weight:

50618.9

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:12010185 ]
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:15894081 ]
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:1683559 ]
4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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. doi: 10.1016/j.talanta.2005.06.027. Epub 2005 Jul 22. [PubMed:18970411 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

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. Promotes cell proliferation

Gene Name:

DRD3

Uniprot ID:

P35462

Molecular weight:

44224.3

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:8301582 ]

Transporters

General function:

Involved in ATP binding

Specific function:

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

Gene Name:

ABCB1

Uniprot ID:

P08183

Molecular weight:

141477.3

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:12954186 ]
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:8647944 ]

PMID: 22588303

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