Domperidone

Overview

Description
A medication used to treat various conditions in the stomach, including heartburn, stomach pain, nausea, and vomiting.
Description
A medication used to treat various conditions in the stomach, including heartburn, stomach pain, nausea, and vomiting.
DrugBank ID
DB01184
Type
Small Molecule
US Approved
NO
Other Approved
YES
Clinical Trials
Phase 0
1
Phase 1
6
Phase 2
12
Phase 3
10
Phase 4
15
Therapeutic Categories
  • Prokinetic Agents
Mechanism of Action

Identification

Summary

Domperidone is a dopamine receptor antagonist used as a peristaltic stimulant and anti-emetic agent for dyspepsia, indigestion, epigastric pain, nausea, and vomiting.

Generic Name
Domperidone
DrugBank Accession Number
DB01184
Background

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.

Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Structure
Weight
Average: 425.911
Monoisotopic: 425.161852744
Chemical Formula
C22H24ClN5O2
Synonyms
  • 1-(3-(4-(5-chloro-2-oxo-2,3-dihydrobenzo[d]imidazol-1-yl)piperidin-1-yl)propyl)-1H-benzo[d]imidazol-2(3H)-one
  • 5-chloro-1-(1-(3-(2-oxo-1-benzimidazolinyl)propyl)-4-piperidyl)-2-benzimidazolinone
  • 5-chloro-1-(1-(3-(2-oxo-2,3-dihydrobenzo[d]imidazol-1-yl)propyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
  • 5-chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one
  • Domperidona
  • Domperidone
  • Domperidonum
External IDs
  • R 33,812
  • R-33812

Pharmacology

Indication

For management of dyspepsia, heartburn, epigastric pain, nausea, and vomiting.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Symptomatic treatment ofDiabetic gastroparesis••••••••••••
Used in combination to treatDyspepsiaCombination Product in combination with: Lansoprazole (DB00448)•••••••••••••••••••
Used in combination to treatDyspepsiaCombination Product in combination with: Lansoprazole (DB00448)•••••••••••••••••••
Used in combination to treatErosive esophagitis (ee)Combination Product in combination with: Dexlansoprazole (DB05351)•••••••••••••••••••
Prophylaxis ofGastrointestinal symptoms••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Domperidone 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 action

Domperidone 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

TargetActionsOrganism
AD(3) dopamine receptor
antagonist
Humans
AD(2) dopamine receptor
antagonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

91%-93%

Metabolism

Hover over products below to view reaction partners

Route of elimination

Not Available

Half-life

7 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Side effects include galactorrhea, gynecomastia, or menstrual irregularities.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

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
AbametapirThe serum concentration of Domperidone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Domperidone can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Domperidone can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Domperidone can be decreased when combined with Acalabrutinib.
AcebutololThe metabolism of Domperidone can be decreased when combined with Acebutolol.
Food Interactions
  • Take before a meal. Take 15-30 minutes before meals.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Domperidone maleate899U5WF46A83898-65-1OAUUYDZHCOULIO-BTJKTKAUSA-N
International/Other Brands
Euciton (Roux-Ocefa) / Moperidona (Sidus) / Motilium (Janssen) / Nauzelin (Kyowa Hakko Kirin)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DomperidoneTablet10 mgOralSivem Pharmaceuticals Ulc1998-09-03Not applicableCanada flag
DomperidoneTablet10 mgOralSun Pharma Canada IncNot applicableNot applicableCanada flag
DomperidoneTablet10 mgOralSanis Health Inc2010-05-12Not applicableCanada flag
Domperidone-10Tablet10 mgOralPro Doc Limitee1998-07-13Not applicableCanada flag
MotilidoneTablet10 mgOralTechnilab Pharma Inc.1997-09-172005-08-05Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-domperidoneTablet10 mgOralApotex Corporation1997-09-17Not applicableCanada flag
Ava-domperidoneTablet10 mgOralAvanstra Inc2011-09-152014-08-21Canada flag
Bio-domperidoneTablet10 mgOralBiomed Pharma2016-04-26Not applicableCanada flag
Dom-domperidoneTablet10 mgOralDominion Pharmacal1998-09-17Not applicableCanada flag
Ftp-domperidone MaleateTablet10 mgOralGmd Distribution Inc.1998-10-092005-08-05Canada flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ออโต้ ซัสเพนชั่นSuspension5 mg/5mLOralบริษัท พาตาร์แลบ (2517) จำกัด จำกัด2013-04-19Not applicableThailand flag
โมแลกซ์ ยาน้ำแขวนตะกอนSuspension5 mg/5mLOralบริษัท สยามเภสัช จำกัด2007-04-18Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DEXGARD 30/30 MG MR KAPSUL, 30 ADETDomperidone (30 mg) + Dexlansoprazole (30 mg)CapsuleOralNUVOMED İLAÇ SAN.TİC. A.Ş.2012-07-31Not applicableTurkey flag
DEXGARD 30/30 MG MR KAPSUL, 60 ADETDomperidone (30 mg) + Dexlansoprazole (30 mg)CapsuleOralNUVOMED İLAÇ SAN.TİC. A.Ş.2012-07-31Not applicableTurkey flag
DEXRIDON MR 30/10 MG KAPSÜL ,30 KAPSÜLDomperidone (30 mg) + Dexrabeprazole (10 mg)CapsuleOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2014-01-08Not applicableTurkey flag
DUEDOM 30/10 MG KAPSÜL, 30 ADETDomperidone (10 mg) + Dexlansoprazole (30 mg)CapsuleOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2011-12-22Not applicableTurkey flag
DUEDOM 60/10 MG KAPSÜL, 30 ADETDomperidone (10 mg) + Dexlansoprazole (60 mg)CapsuleOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2011-12-22Not applicableTurkey flag

Categories

ATC Codes
A03FA03 — Domperidone
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
show 3 more
Substituents
Amine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid / Benzimidazole / Heteroaromatic compound / Hydrocarbon derivative
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzimidazoles, heteroarylpiperidine (CHEBI:31515)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
5587267Z69
CAS number
57808-66-9
InChI Key
FGXWKSZFVQUSTL-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

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 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. [Article]
  2. TITCK Product Information: Duedom (dexlansoprazole/domperidone) oral capsules [Link]
Human Metabolome Database
HMDB0015315
KEGG Drug
D01745
PubChem Compound
3151
PubChem Substance
46508314
ChemSpider
3039
BindingDB
50241107
RxNav
3626
ChEBI
31515
ChEMBL
CHEMBL219916
ZINC
ZINC000004175569
Therapeutic Targets Database
DAP001368
PharmGKB
PA134711056
Guide to Pharmacology
GtP Drug Page
Wikipedia
Domperidone
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableAvailableNot AvailableGastroparesis1somestatusstop reasonjust information to hide
Not AvailableAvailableNot AvailableOncology Patients With Gastroparesis1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableArrhythmia1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableBreast Milk Production / Breastfeeding / Sudden Cardiac Death / Ventricular Tachyarrhythmias1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableParkinson's Disease (PD)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Professional Co.
Dosage Forms
FormRouteStrength
Tablet, effervescent
CapsuleOral
Solution / drops; suspension / drops5 MG/5ML
Tablet, soluble
SuspensionOral0.1 g
SuspensionOral100 mg
SuspensionOral
SuspensionOral0.1 %
SuspensionOral5 mg
SyrupOral
SyrupOral5 mg/ml
Solution / dropsOral1 %
SuppositoryRectal60 MG
SyrupOral0.1 %
Granule, effervescent5 MG
Tablet, chewableOral5 MG
SuspensionOral6.36 mg
TabletOral12.7 mg
TabletOral12.73 MG
TabletOral12725 MG
Tablet, film coatedOral12.73 MG
Tablet, effervescent10 MG
Tablet, film coatedOral10 mg/tablet
Tablet, film coatedOral13 MG
Tablet, chewableOral
Tablet, effervescent5 MG
SuspensionOral
TabletOral
Pill
Tablet, film coatedOral
Capsule, delayed release pelletsOral30 mg
Granule, effervescent10 MG
InjectionIntramuscular; Intravenous10 mg/2ml
InjectionIntramuscular; Intravenous4 mg/2ml
Solution / dropsOral10 mg/ml
Solution / dropsOral20 mg/ml
Solution / dropsOral20 ML
SuspensionOral0.1000 mg
SyrupOral1 MG/ML
TabletOral20 MG
SuspensionOral1 mg/ml
Tablet, orally disintegrating
Granule, effervescent
Solution / dropsOral
SuppositoryRectal10 MG
SuppositoryRectal30 MG
Tablet, coatedOral
TabletOral10.00 mg
Solution / drops; suspension / drops
TabletOral10.000 mg
TabletOral10000 MG
Solution / drops; suspension / drops5 MG/ML
SuspensionOral5 MG/ML
SyrupOral5 mg/5ml
Tablet, soluble10 MG
TabletOral
Tablet, film coatedOral10 mg
Tablet, coatedOral10 mg
SuspensionOral5 mg/5ml
TabletOral10 mg
Prices
Unit descriptionCostUnit
Domperidone bp powder55.2USD g
Ratio-Domperidone Maleate 10 mg Tablet0.16USD tablet
Apo-Domperidone 10 mg Tablet0.16USD tablet
Mylan-Domperidone 10 mg Tablet0.16USD tablet
Novo-Domperidone 10 mg Tablet0.16USD tablet
Nu-Domperidone 10 mg Tablet0.16USD tablet
Pms-Domperidone 10 mg Tablet0.15USD tablet
Ran-Domperidone 10 mg Tablet0.15USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)242.5 °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 Solubility0.0925 mg/mLALOGPS
logP3.7ALOGPS
logP2.9Chemaxon
logS-3.7ALOGPS
pKa (Strongest Acidic)12.52Chemaxon
pKa (Strongest Basic)7.03Chemaxon
Physiological Charge0Chemaxon
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
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9967
Blood Brain Barrier+0.8686
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7029
P-glycoprotein inhibitor IInhibitor0.7244
P-glycoprotein inhibitor IIInhibitor0.628
Renal organic cation transporterInhibitor0.6546
CYP450 2C9 substrateNon-substrate0.7974
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.6392
CYP450 1A2 substrateInhibitor0.8737
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.5577
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8695
Ames testNon AMES toxic0.6608
CarcinogenicityNon-carcinogens0.922
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9828 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7527
hERG inhibition (predictor II)Inhibitor0.917
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-MSsplash10-08mj-2692000000-9daf8802fe5fc021ea4f
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-004i-0300900000-912de932579a7a2a6e2f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00xr-0700900000-fbaf0980af220c88125f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0300900000-912de932579a7a2a6e2f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0900300000-877326ac38180c1229cd
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0010900000-e57f6e2ee6aacbedd7a3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ae9-0005900000-18cac961081a0dbc5aae
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a7i-0009700000-a39c00396423f5ac88b8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0019200000-7ae904027d95e5c04121
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-003r-0339100000-c5a3385768cb07cef014
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001l-9414100000-50682645b39f4fd6bd8e
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-210.1130203
predicted
DarkChem Lite v0.1.0
[M-H]-194.61037
predicted
DeepCCS 1.0 (2019)
[M+H]+208.9825203
predicted
DarkChem Lite v0.1.0
[M+H]+196.96837
predicted
DeepCCS 1.0 (2019)
[M+Na]+208.9953203
predicted
DarkChem Lite v0.1.0
[M+Na]+203.54161
predicted
DeepCCS 1.0 (2019)

Targets

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Details
1. D(3) dopamine receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation
Specific Function
dopamine neurotransmitter receptor activity, coupled via Gi/Go
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44194.315 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity)
Specific Function
dopamine binding
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
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. [Article]
  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. [Article]
  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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. [Article]
  6. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 Da
References
  1. Ward BA, Morocho A, Kandil A, Galinsky RE, Flockhart DA, Desta Z: Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol. 2004 Sep;58(3):277-87. doi: 10.1111/j.1365-2125.2004.02156.x. [Article]
  2. Domperidone 10mg Tablets - Summary of Product Characteristics - eMC [Link]
  3. Domperidone FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Ward BA, Morocho A, Kandil A, Galinsky RE, Flockhart DA, Desta Z: Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol. 2004 Sep;58(3):277-87. doi: 10.1111/j.1365-2125.2004.02156.x. [Article]
  2. Braun M, Cawello W, Boekens H, Horstmann R: Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine. Br J Clin Pharmacol. 2009 Feb;67(2):209-15. doi: 10.1111/j.1365-2125.2008.03334.x. Epub 2008 Dec 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Ward BA, Morocho A, Kandil A, Galinsky RE, Flockhart DA, Desta Z: Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol. 2004 Sep;58(3):277-87. doi: 10.1111/j.1365-2125.2004.02156.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Ward BA, Morocho A, Kandil A, Galinsky RE, Flockhart DA, Desta Z: Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol. 2004 Sep;58(3):277-87. doi: 10.1111/j.1365-2125.2004.02156.x. [Article]
  2. Braun M, Cawello W, Boekens H, Horstmann R: Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine. Br J Clin Pharmacol. 2009 Feb;67(2):209-15. doi: 10.1111/j.1365-2125.2008.03334.x. Epub 2008 Dec 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. [Article]
  2. 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. [Article]
  3. Michaud V, Simard C, Turgeon J: Characterization of CYP3A isozymes involved in the metabolism of domperidone: role of cytochrome b5 and inhibition by ketoconazole. Drug Metab Lett. 2010 Apr;4(2):95-103. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. Health Canada Approved Drug Products: Domperidone Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
Specific Function
all-trans retinoic acid 18-hydroxylase activity
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57469.95 Da
References
  1. Flockhart Table of Drug Interactions [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
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. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 06, 2024 16:18