DT-Web

DB00800 - Fenoldopam


Identification
Name Fenoldopam
Accession Number DB00800 (APRD00969)
Type small molecule
Description A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 305.756
Groups approved
Monoisotopic Weight 305.08187109
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.
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.
Absorption Not Available
Protein binding Not Available
Biotransformation 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.
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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


D(1B) dopamine receptor
Name D(1B) dopamine receptor
Gene Name DRD5
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
  • 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
DTHybrid score 0.2559
D(1A) dopamine receptor
Name D(1A) dopamine receptor
Gene Name DRD1
Pharmacological action yes
Actions agonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • 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
  • 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
DTHybrid score 0.3644
Alpha-2B adrenergic receptor
Name Alpha-2B adrenergic receptor
Gene Name ADRA2B
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 0.3545
Alpha-2C adrenergic receptor
Name Alpha-2C adrenergic receptor
Gene Name ADRA2C
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 0.3462
Alpha-2A adrenergic receptor
Name Alpha-2A adrenergic receptor
Gene Name ADRA2A
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 0.4973

Predictions


Id Partner name Gene Name Score
831 D(2) dopamine receptor DRD2 0.2522
556 Alpha-1A adrenergic receptor ADRA1A 0.2142
502 5-hydroxytryptamine 2A receptor HTR2A 0.1933
432 D(4) dopamine receptor DRD4 0.1732
638 D(3) dopamine receptor DRD3 0.1663
320 5-hydroxytryptamine 1A receptor HTR1A 0.1603
590 5-hydroxytryptamine 2C receptor HTR2C 0.1529
632 Alpha-1B adrenergic receptor ADRA1B 0.1336
725 5-hydroxytryptamine 1D receptor HTR1D 0.1326
4119 Cytochrome P450 2D6 CYP2D6 0.1255
885 5-hydroxytryptamine 1B receptor HTR1B 0.1217
4512 Cytochrome P450 3A4 CYP3A4 0.1157
436 5-hydroxytryptamine 2B receptor HTR2B 0.1025
4200 Cytochrome P450 1A2 CYP1A2 0.1018
789 Alpha-1D adrenergic receptor ADRA1D 0.0816
716 5-hydroxytryptamine 7 receptor HTR7 0.0752
492 Histamine H1 receptor HRH1 0.0703
6145 Solute carrier family 22 member 1 SLC22A1 0.0491
1588 Multidrug resistance protein 1 ABCB1 0.0479
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0475
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0462
1256 5-hydroxytryptamine 6 receptor HTR6 0.0444
274 Muscarinic acetylcholine receptor M5 CHRM5 0.043
766 Beta-2 adrenergic receptor ADRB2 0.043
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0418
193 Beta-1 adrenergic receptor ADRB1 0.0414
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0398
6070 Nischarin NISCH 0.0397
824 Sodium-dependent serotonin transporter SLC6A4 0.0377
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0373
6147 Solute carrier family 22 member 3 SLC22A3 0.0368
528 5-hydroxytryptamine 1E receptor HTR1E 0.0352
3941 Amine oxidase [flavin-containing] A MAOA 0.0343
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.034
6144 Solute carrier family 22 member 2 SLC22A2 0.0325
4118 Cytochrome P450 3A5 CYP3A5 0.0323
713 Sodium-dependent dopamine transporter SLC6A3 0.0322
341 5-hydroxytryptamine 3 receptor HTR3A 0.0299
6016 Cytochrome P450 2C19 CYP2C19 0.0277
1517 Beta-3 adrenergic receptor ADRB3 0.0265
6020 Aldehyde oxidase AOX1 0.0258
131 Synaptic vesicular amine transporter SLC18A2 0.0256
4757 Cytochrome P450 2C9 CYP2C9 0.0249
118 Organic cation/carnitine transporter 2 SLC22A5 0.0241
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0237
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0235
6107 Cytochrome P450 3A7 CYP3A7 0.0234
3939 Amine oxidase [flavin-containing] B MAOB 0.0213
828 Phenylalanine-4-hydroxylase PAH 0.0211
3109 Phenylalanine-4-hydroxylase phhA 0.0211
6013 Cytochrome P450 2E1 CYP2E1 0.0201
587 Serum albumin ALB 0.0179
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0176
465 Calmodulin CALM1 0.0162
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0152
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0146
6151 Monocarboxylate transporter 10 SLC16A10 0.0135
3810 Catechol O-methyltransferase COMT 0.0132
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0128
6024 Cytochrome P450 1A1 CYP1A1 0.0126
124 Histamine H2 receptor HRH2 0.0126
1636 Trace amine-associated receptor 1 TAAR1 0.011
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0104
3426 Glutamine synthetase glnA 0.0103
3987 Glutamine synthetase GLUL 0.0103
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0102
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.01
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0097
3923 Cholinesterase BCHE 0.0092
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0089
6030 Cytochrome P450 2B6 CYP2B6 0.0078
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0073
233 Potassium channel subfamily K member 2 KCNK2 0.0072
4924 Cytochrome P450 2C8 CYP2C8 0.007
833 Organic cation/carnitine transporter 1 SLC22A4 0.0069
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0067
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0064
153 Dopamine beta-hydroxylase DBH 0.0062
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0061
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0061
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0061
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0059
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0057
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0056
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0054
3811 Cytochrome P450 19A1 CYP19A1 0.0052
164 Histamine H4 receptor HRH4 0.005
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0048
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0048
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0047
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0046
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0042
4120 NADPH--cytochrome P450 reductase POR 0.0037
1898 Cytochrome P450 1B1 CYP1B1 0.0029
696 Kappa-type opioid receptor OPRK1 0.0026
5718 Cytochrome P450 2A6 CYP2A6 0.0025
6106 Cytochrome P450 2C18 CYP2C18 0.0024
474 Acetylcholinesterase ACHE 0.0023
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0022
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0021
1656 CYP2B protein CYP2B 0.0021
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0016
776 Bile salt export pump ABCB11 0.0015
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0013
1618 High affinity nerve growth factor receptor NTRK1 0.001
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.001
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.001
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.001
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0008
467 Delta-type opioid receptor OPRD1 0.0007
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