Identification

Name
Fenoldopam
Accession Number
DB00800  (APRD00969)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • Fénoldopam
  • Fenoldopam
  • Fenoldopamum
External IDs
SKF 82526 / SKF 82526-J
Product Ingredients
IngredientUNIICASInChI Key
Fenoldopam mesylateHA3R0MY01667227-57-0CVKUMNRCIJMVAR-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CorlopamInjection, solution10 mg/1mLIntravenousHospira, Inc.2005-02-28Not applicableUs
CorlopamInjection, solution10 mg/1mLIntravenousHospira, Inc.2008-03-142013-12-01Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fenoldopam MesylateInjection10 mg/1mLIntravenousBedford Pharmaceuticals2004-10-142010-05-31Us
Fenoldopam MesylateInjection, solution10 mg/1mLIntravenousSandoz2005-02-152009-05-31Us
Fenoldopam MesylateInjection10 mg/1mLIntravenousBedford Pharmaceuticals2004-10-142010-05-31Us
Categories
UNII
INU8H2KAWG
CAS number
67227-56-9
Weight
Average: 305.756
Monoisotopic: 305.08187109
Chemical Formula
C16H16ClNO3
InChI Key
TVURRHSHRRELCG-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

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Fenoldopam is an agonist at D1-like dopamine receptors, binds to α2-adrenoceptors, increasing renal blood flow.

Mechanism of action

Fenoldopam 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.

TargetActionsOrganism
AD(1B) dopamine receptor
agonist
Human
AD(1A) dopamine receptor
agonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
inhibitor
Human
UAlpha-1D adrenergic receptor
inhibitor
Human
UAlpha-1A adrenergic receptor
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not 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 elimination

Radiolabeled 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 life

The elimination half-life is about 5 minutes in mild to moderate hypertensives, with little difference between the R (active) and S isomers.

Clearance
Not Available
Toxicity

The 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirFenoldopam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Fenoldopam which could result in a higher serum level.
AcebutololThe risk or severity of adverse effects can be increased when Fenoldopam is combined with Acebutolol.
AceclofenacThe therapeutic efficacy of Fenoldopam can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Fenoldopam can be decreased when used in combination with Acemetacin.
AcetaminophenAcetaminophen may decrease the excretion rate of Fenoldopam which could result in a higher serum level.
Acetylsalicylic acidThe therapeutic efficacy of Fenoldopam can be decreased when used in combination with Acetylsalicylic acid.
AclidiniumFenoldopam may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineFenoldopam may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Fenoldopam which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference
US4197297
General References
Not Available
External Links
Human Metabolome Database
HMDB0014938
KEGG Drug
D00613
KEGG Compound
C07693
PubChem Compound
3341
PubChem Substance
46504963
ChemSpider
3224
BindingDB
60917
ChEBI
5002
ChEMBL
CHEMBL588
Therapeutic Targets Database
DAP000254
PharmGKB
PA164784034
IUPHAR
939
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Wikipedia
Fenoldopam
ATC Codes
C01CA19 — Fenoldopam
FDA label
Download (239 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Unknown StatusTreatmentHigh Blood Pressure (Hypertension)1
2CompletedPreventionAcute Renal Failure (ARF) / Cardiac Surgical Procedures / Chronic Renal Failure (CRF)1
2CompletedTreatmentCardiac Surgery With Cardiopulmonary Bypass1
2, 3Not Yet RecruitingPreventionAcute Kidney Injury (AKI) / Patent Ductus Arteriosus (PDA)1
3CompletedTreatmentAcute Renal Failure (ARF)2
3TerminatedPreventionAcute Renal Failure (ARF)1
4CompletedPreventionCardiac Complications / Cardiopulmonary Bypass1
4Unknown StatusTreatmentCoronary Artery Disease1
4WithdrawnTreatmentAcute Renal Failure (ARF)1
Not AvailableCompletedNot AvailableSalt-sensitive Hypertension1
Not AvailableTerminatedPreventionPartial Nephrectomy1

Pharmacoeconomics

Manufacturers
  • Hospira inc
  • Bedford laboratories
  • Pharmaforce inc
  • Sandoz canada inc
  • Teva parenteral medicines inc
Packagers
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Hospira Inc.
  • Sandoz
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
InjectionIntravenous10 mg/1mL
Injection, solutionIntravenous10 mg/1mL
Prices
Unit descriptionCostUnit
Fenoldopam 10 mg/ml ampule213.75USD ml
Corlopam 10 mg/ml ampul81.9USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility4000 mg/LNot Available
logP2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.272 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9972
Blood Brain Barrier+0.7784
Caco-2 permeable-0.5345
P-glycoprotein substrateSubstrate0.8329
P-glycoprotein inhibitor INon-inhibitor0.9142
P-glycoprotein inhibitor IINon-inhibitor0.8567
Renal organic cation transporterNon-inhibitor0.6062
CYP450 2C9 substrateNon-substrate0.8216
CYP450 2D6 substrateNon-substrate0.7124
CYP450 3A4 substrateNon-substrate0.5301
CYP450 1A2 substrateNon-inhibitor0.713
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8316
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7436
Ames testNon AMES toxic0.7166
CarcinogenicityNon-carcinogens0.9006
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.7788 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6864
hERG inhibition (predictor II)Inhibitor0.8833
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0429000000-b564c6e7915f2c21d65e

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Not Available
Direct Parent
Benzazepines
Alternative Parents
Azepines / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Benzene and substituted derivatives / Aryl chlorides / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organochlorides
show 1 more
Substituents
Benzazepine / 1-hydroxy-2-unsubstituted benzenoid / Azepine / Aralkylamine / Phenol / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Azacycle
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzazepine (CHEBI:5002)

Targets

Details
1. D(1B) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD5
Uniprot ID
P21918
Uniprot Name
D(1B) dopamine receptor
Molecular Weight
52950.5 Da
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:17139284]
  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:17016423]
  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. doi: 10.1097/HJH.0b013e3283293c7b. [PubMed:19293728]
  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:8103596]
Details
2. D(1A) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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. doi: 10.1097/HJH.0b013e3283293c7b. [PubMed:19293728]
  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:8103596]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
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:17139284]
  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:17016423]
  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:7670737]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
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:17139284]
  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:17016423]
  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:7670737]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
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:17139284]
  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:17016423]
  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:7670737]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
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:7670737]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
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:7670737]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
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:7670737]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:44