FENOLDOPAM

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H16ClNO3
Molecular Weight	305.756
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC=C(C=C1)C2CNCCC3=C(Cl)C(O)=C(O)C=C23

InChI

InChIKey=TVURRHSHRRELCG-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf | https://www.drugbank.ca/drugs/DB00800

Fenoldopam (marketed under the brand name Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist. 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. Fenoldopam Mesylate Injection, USP is indicated 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D1 receptor 106 Target ID: CHEMBL2056 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9784114 \| https://www.ncbi.nlm.nih.gov/pubmed/7525564	Agonist 2752		40.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf	Primary		Approved 8583	CORLOPAM Approved Use Adult Patients: Fenoldopam is indicated 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. Transition to oral therapy with another agent can begin at any time after blood pressure is stable during fenoldopam infusion. Pediatric Patients: Fenoldopam is indicated for the in-hospital, short-term (up to 4 hours) reduction in blood pressure. Launch Date 1997

C_max

Value	Dose	Co-administered	Analyte	Population
26.5 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1673097	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOLDOPAM plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FASTED
10.9 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1673097	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOLDOPAM plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
44.7 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1673097	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOLDOPAM plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FASTED
26.8 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1673097	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOLDOPAM plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1673097	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOLDOPAM plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FASTED
2.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1673097	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOLDOPAM plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
1.5 ug/kg/min single, intravenous Highest studied dose Dose: 1.5 ug/kg/min Route: intravenous Route: single Dose: 1.5 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/1967592	unhealthy, 46±3 Health Status: unhealthy Age Group: 46±3 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1967592	Sources: https://pubmed.ncbi.nlm.nih.gov/1967592
0.8 ug/kg/min single, intravenous Recommended Dose: 0.8 ug/kg/min Route: intravenous Route: single Dose: 0.8 ug/kg/min Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf	Disc. AE: Tachycardia, Hypokalemia... AEs leading to discontinuation/dose reduction: Tachycardia Hypokalemia Anaphylactic reaction Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf

AEs

AE	Significance	Dose	Population
Anaphylactic reaction	Disc. AE	0.8 ug/kg/min single, intravenous Recommended Dose: 0.8 ug/kg/min Route: intravenous Route: single Dose: 0.8 ug/kg/min Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf
Hypokalemia	Disc. AE	0.8 ug/kg/min single, intravenous Recommended Dose: 0.8 ug/kg/min Route: intravenous Route: single Dose: 0.8 ug/kg/min Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf
Tachycardia	Disc. AE	0.8 ug/kg/min single, intravenous Recommended Dose: 0.8 ug/kg/min Route: intravenous Route: single Dose: 0.8 ug/kg/min Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019922s016lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP3 246 BSEP 550 MRP4 290 CYP2C19 2057 CYP1A2 2153 MRP2 499 CYP19A1 429	SULT 12 COMT 8 CYP 303 UGT 219

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170465321	inconclusive [IC50 10.964 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671197#sid=170465321	no [IC50 9.7717 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	no [IC50 >1000 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144203703	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671199#sid=170465321	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170465321	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170465321	no

Drug as victim

Target	Modality	Activity
CYP 303	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/019922s019lbl.pdf#page=11 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/019922ap_corlopam_clinphrmr.pdf#page=35 Page: 11, (ClinP) 35	no
COMT 8	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/019922ap_corlopam_clinphrmr.pdf#page=35 Page: 35-46	yes
SULT 12	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/019922s019lbl.pdf#page=11 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/019922ap_corlopam_clinphrmr.pdf#page=35 Page: 11, (ClinP) 35-46	yes
UGT 219	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/019922s019lbl.pdf#page=11 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/019922ap_corlopam_clinphrmr.pdf#page=35 Page: 11, (ClinP) 35-46	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=50106351 \| https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=26752227

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5002	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5002
ChemicalBook	CB6729842	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6729842
eMolecules	36518021	https://www.emolecules.com/cgi-bin/more?vid=36518021
MolPort	MolPort-006-167-637	https://www.molport.com/shop/molecule-link/MolPort-006-167-637
Selleck Chemicals	fenoldopam-corlopam	http://www.selleckchem.com/products/fenoldopam-corlopam.html

PubMed

Title	Date	PubMed
Design and rationale of CONTRAST--a prospective, randomized, placebo-controlled trial of fenoldopam mesylate for the prevention of radiocontrast nephropathy.	2001	12439366
Hypertensive emergencies.	2001 Apr	11450325
Use of fenoldopam to prevent radiocontrast nephropathy in high-risk patients.	2001 Jul	11458411
Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.	2001 Jul	11429337
Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature.	2002 Dec	12472930
Effects of fenoldopam, a dopamine D-1 agonist, and clevidipine, a calcium channel antagonist, in acute renal failure in anesthetized rats.	2002 May	12069360
Fenoldopam mesylate blocks reductions in renal plasma flow after radiocontrast dye infusion: a pilot trial in the prevention of contrast nephropathy.	2002 May	12040355
The third strike.	2002 Nov	12410498
Contrast nephropathy : an evidence-based approach to prevention.	2003	14728060
Hypertensive emergencies. Etiology and management.	2003	14727943
A review of pharmacologic interventions to prevent contrast-induced nephropathy.	2003	14668708
A review of contemporary prevention strategies for radiocontrast nephropathy: a focus on fenoldopam and N-acetylcysteine.	2003	12556733
Pharmacologic identification of putative D1 dopamine receptors in feline kidneys.	2003 Aug	12887611
The International Sepsis Forum's controversies in sepsis: my initial vasopressor agent in septic shock is dopamine rather than norepinephrine.	2003 Feb	12617729
Fenoldopam--but not dopamine--selectively increases gastric mucosal oxygenation in dogs.	2003 Jul	12847395
In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery.	2004 Aug	15169740
N-Acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity.	2004 Aug 18	15312855
American society of nephrology-36th annual meeting and renal week 2003.	2004 Jan	14968812
Optimization of intestinal mucosal oxygenation in shock: a role for medical therapy?	2004 Jan	14707603
Prevention of radiocontrast-induced nephropathy.	2004 Jul	15211433
Lessons in formulary management: the case of fenoldopam for radiographic contrast material-induced nephropathy.	2004 Jun	15222676
Prophylaxis of iodinated contrast media-induced nephropathy: a pharmacological point of view.	2004 Mar	15076008
Dopamine D1 receptor augmentation of D3 receptor action in rat aortic or mesenteric vascular smooth muscles.	2004 Mar	14769810
Aberrant D1 and D3 dopamine receptor transregulation in hypertension.	2004 Mar	14732731
Prevention of contrast media nephrotoxicity--the story so far.	2004 May	15081843
Fenoldopam versus nitroprusside for the treatment of hypertensive emergency.	2004 May	15039472

Patents

Sample Use Guides

In Vivo Use Guide

Adults: Initiate dosing at 0.01 to 0.3 mcg/kg/min by continuous infusion. Dosing can be increased in increments of 0.05 to 0.1 mcg/kg/minute every 15 minutes or longer until target blood pressure is reached. Dilute prior to administration Pediatrics: Initiate dosing at 0.2 mcg/kg/minute by continuous infusion and titrate dose by 0.3 to 0.5 mcg/kg/min every 20-30 minutes to a maximum dose of 0.8 mcg/kg/minute

Route of Administration: Intravenous

In Vitro Use Guide

Incubation of freshly isolated mouse kidney slices with the selective D(1)-like receptor agonists fenoldopam (10 uM) and SKF-38393 (10 uM) for 1 h induced NaPi-IIa internalization and reduced expression of NaPi-IIa in the brush border membrane (BBM).

Name

Type

Language

FENOLDOPAM

Official Name

English

CARLACOR

Preferred Name

English

FENOLDOPAM [MI]

Common Name

English

Fenoldopam [WHO-DD]

Common Name

English

fenoldopam [INN]

Common Name

English

FENOLDOPAM [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884