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Identification
NameFenoldopam
Accession NumberDB00800  (APRD00969)
TypeSmall Molecule
GroupsApproved
Description

A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
FenoldopamGermanINN
FénoldopamFrenchINN
FenoldopamSpanishINN
FenoldopamumLatinINN
Salts
Name/CAS Structure Properties
Fenoldopam Mesilate
Thumb Not applicable DBSALT000946
Fenoldopam Mesylate
Thumb Not applicable DBSALT000945
Brand names
NameCompany
CorlopamHospira
Brand mixturesNot Available
Categories
CAS number67227-57-0
WeightAverage: 305.756
Monoisotopic: 305.08187109
Chemical FormulaC16H16ClNO3
InChI KeyTVURRHSHRRELCG-UHFFFAOYSA-N
InChI
InChI=1S/C16H16ClNO3/c17-15-11-5-6-18-8-13(9-1-3-10(19)4-2-9)12(11)7-14(20)16(15)21/h1-4,7,13,18-21H,5-6,8H2
IUPAC Name
6-chloro-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
SMILES
OC1=CC=C(C=C1)C1CNCCC2=C(Cl)C(O)=C(O)C=C12
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzazepines
SubclassNot Available
Direct parentBenzazepines
Alternative parents3-Chlorocatechols; o-Chlorophenols; m-Chlorophenols; Chlorobenzenes; Azepines; Aryl Chlorides; Polyols; Dialkylamines; Enols; Polyamines; Organochlorides
Substituentschlorocatechol; 3-chlorocatechol; 3-chlorophenol; 2-chlorophenol; 2-halophenol; 3-halophenol; 1,2-diphenol; azepine; chlorobenzene; phenol derivative; aryl halide; benzene; aryl chloride; polyol; polyamine; secondary amine; enol; secondary aliphatic amine; organohalogen; organochloride; organonitrogen compound; amine
Classification descriptionThis compound belongs to the benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom).
Pharmacology
IndicationFor the in-hospital, short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end-organ function.
PharmacodynamicsFenoldopam is an agonist at D1-like dopamine receptors, binds to α2-adrenoceptors, increasing renal blood flow.
Mechanism of actionFenoldopam is a rapid-acting vasodilator. It is an agonist for D1-like dopamine receptors and binds with moderate affinity to α2-adrenoceptors. It has no significant affinity for D2-like receptors, α1 and β-adrenoceptors, 5HT1 and 5HT2 receptors, or muscarinic receptors. Fenoldopam is a racemic mixture with the R-isomer responsible for the biological activity. The R-isomer has approximately 250-fold higher affinity for D1-like receptors than does the S-isomer. In non-clinical studies, fenoldopam had no agonist effect on presynaptic D2-like dopamine receptors, or α or β -adrenoceptors, nor did it affect angiotensin-converting enzyme activity. Fenoldopam may increase norepinephrine plasma concentration.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Elimination is largely by conjugation, without participation of cytochrome P-450 enzymes. Methylation, glucuronidation, and sulfation are the main routes of conjugation.

Route of eliminationRadiolabeled studies show that about 90% of infused fenoldopam is eliminated in urine, 10% in feces. Elimination is largely by conjugation, without participation of cytochrome P-450 enzymes. Only 4% of the administered dose is excreted unchanged.
Half lifeThe elimination half-life is about 5 minutes in mild to moderate hypertensives, with little difference between the R (active) and S isomers.
ClearanceNot Available
ToxicityThe most likely reaction of overdose would be excessive hypotension which should be treated with drug discontinuation and appropriate supportive measures.
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 + 0.9972
Blood Brain Barrier + 0.7784
Caco-2 permeable - 0.5345
P-glycoprotein substrate Substrate 0.8329
P-glycoprotein inhibitor I Non-inhibitor 0.9142
P-glycoprotein inhibitor II Non-inhibitor 0.8567
Renal organic cation transporter Non-inhibitor 0.6062
CYP450 2C9 substrate Non-substrate 0.8216
CYP450 2D6 substrate Non-substrate 0.7124
CYP450 3A4 substrate Non-substrate 0.5301
CYP450 1A2 substrate Non-inhibitor 0.713
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8316
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7436
Ames test Non AMES toxic 0.7166
Carcinogenicity Non-carcinogens 0.9006
Biodegradation Not ready biodegradable 0.9935
Rat acute toxicity 2.7788 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6864
hERG inhibition (predictor II) Inhibitor 0.8833
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • Bedford laboratories
  • Pharmaforce inc
  • Sandoz canada inc
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravenous drip
Prices
Unit descriptionCostUnit
Fenoldopam 10 mg/ml ampule213.75USDml
Corlopam 10 mg/ml ampul81.9USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility4000 mg/LNot Available
logP2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.272ALOGPS
logP2.39ALOGPS
logP1.92ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)8.12ChemAxon
pKa (Strongest Basic)10.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area72.72 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity82.68 m3·mol-1ChemAxon
Polarizability30.71 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4197297
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00613
PubChem Compound3341
PubChem Substance46504963
ChemSpider3224
ChEBI5002
ChEMBLCHEMBL588
Therapeutic Targets DatabaseDAP000254
PharmGKBPA164784034
IUPHAR939
Guide to Pharmacology939
RxListhttp://www.rxlist.com/cgi/generic3/fenoldopam.htm
WikipediaFenoldopam
ATC CodesC01CA19
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(239 KB)
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. D(1B) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(1B) dopamine receptor P21918 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. Zeng C, Han Y, Huang H, Yu C, Ren H, Shi W, He D, Huang L, Yang C, Wang X, Zhou L, Jose PA: D1-like receptors inhibit insulin-induced vascular smooth muscle cell proliferation via down-regulation of insulin receptor expression. J Hypertens. 2009 May;27(5):1033-41. Pubmed
  4. Dhasmana KM, Villalon CM, Zhu YN, Parmar SS: The role of dopamine (D2), alpha and beta-adrenoceptor receptors in the decrease in gastrointestinal transit induced by dopamine and dopamine-related drugs in the rat. Pharmacol Res. 1993 May-Jun;27(4):335-47. Pubmed

2. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 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. Zeng C, Han Y, Huang H, Yu C, Ren H, Shi W, He D, Huang L, Yang C, Wang X, Zhou L, Jose PA: D1-like receptors inhibit insulin-induced vascular smooth muscle cell proliferation via down-regulation of insulin receptor expression. J Hypertens. 2009 May;27(5):1033-41. Pubmed
  3. Dhasmana KM, Villalon CM, Zhu YN, Parmar SS: The role of dopamine (D2), alpha and beta-adrenoceptor receptors in the decrease in gastrointestinal transit induced by dopamine and dopamine-related drugs in the rat. Pharmacol Res. 1993 May-Jun;27(4):335-47. Pubmed

3. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 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. Martin SW, Broadley KJ: Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade. Br J Pharmacol. 1995 May;115(2):349-55. Pubmed

4. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 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. Martin SW, Broadley KJ: Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade. Br J Pharmacol. 1995 May;115(2):349-55. Pubmed

5. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 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. Martin SW, Broadley KJ: Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade. Br J Pharmacol. 1995 May;115(2):349-55. Pubmed

6. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

References:

  1. Martin SW, Broadley KJ: Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade. Br J Pharmacol. 1995 May;115(2):349-55. Pubmed

7. Alpha-1D adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Alpha-1D adrenergic receptor P25100 Details

References:

  1. Martin SW, Broadley KJ: Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade. Br J Pharmacol. 1995 May;115(2):349-55. Pubmed

8. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

References:

  1. Martin SW, Broadley KJ: Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade. Br J Pharmacol. 1995 May;115(2):349-55. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:23