Fenoldopam (SKF-82526) is a synthetic benzazepine analog acting as a selective D1 receptor partial agonist. In September 1997, the Food and Drug Administration (FDA) authorized it as an antihypertensive medication. Given that fenoldopam is the only intravenous medication known to enhance renal perfusion, it is theoretically advantageous for hypertensive patients who also have renal insufficiency.

Physicochemical Properties

Molecular Formula	C16H16CLNO3
Molecular Weight	305.75614
Exact Mass	305.081
CAS #	67227-56-9
Related CAS #	Fenoldopam mesylate; 67227-57-0; Fenoldopam hydrochloride; 181217-39-0
PubChem CID	3341
Appearance	Typically exists as solid at room temperature
Density	1.4±0.1 g/cm3
Boiling Point	522.6±50.0 °C at 760 mmHg
Flash Point	269.9±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.656
LogP	1.72
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	21
Complexity	348
Defined Atom Stereocenter Count	0
SMILES	OC1=C(O)C=C2C(C3=CC=C(O)C=C3)CNCCC2=C1Cl
InChi Key	TVURRHSHRRELCG-UHFFFAOYSA-N
InChi Code	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
Chemical Name	9-chloro-5-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
Synonyms	SKF 82526; Fenoldopam
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	DA1 receptor ( EC50 = 55.5 nM )
ADME/Pharmacokinetics	Absorption, Distribution and Excretion 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. Metabolism / Metabolites Elimination is largely by conjugation, without participation of cytochrome P-450 enzymes. Methylation, glucuronidation, and sulfation are the main routes of conjugation. Biological 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.
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of fenoldopam during breastfeeding. The manufacturer recommends avoiding breastfeeding during fenoldopam use; however, because of its poor oral bioavailability and short half-life, any fenoldopam in milk is unlikely to adversely affect the breastfed infant. Also, fenoldopam can be given intravenously to infants. Unlike dopamine, it does not decrease serum prolactin concentrations and might not interfere with nursing. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information in nursing mothers was not found as of the revision date. Unlike dopamine, fenoldopam infusion does not affect serum prolactin concentration in normal women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
References	[1]. Fenoldopam is a partial agonist at dopamine-1 (DA1) receptors in LLC-PK1 cells. J Pharmacol Exp Ther, 1991. 258(1): p. 193-8. [2]. The pharmacology of fenoldopam. Am J Hypertens, 1990. 3(6 Pt 2): p. 116S-119S.
Additional Infomation	Fenoldopam is a benzazepine. It has a role as a dopaminergic antagonist, a vasodilator agent, an alpha-adrenergic agonist, a dopamine agonist and an antihypertensive agent. A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation. Fenoldopam is a Dopaminergic Agonist. The mechanism of action of fenoldopam is as a Dopamine Agonist. Fenoldopam is a benzazepine derivative with vasodilatory and antihypertensive properties. Fenoldopam, a dopamine (DA) receptor agonist, binds specifically to peripheral DA1 receptors and to alpha-2 adrenoceptors with moderate affinity. However, this agent exhibits no significant affinity to DA2, other alpha adrenergic, beta adrenergic, muscarinic, or serotonergic receptors. Receptor binding modulates the transmembrane flux of ions, thereby stimulating adenylate cyclase activity, as well as the release of prolactin. This results in vasodilatation, increased renal blood flow thereby enhancing natriuresis and diuresis leading to a lowering in diastolic blood pressure. A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation. See also: Fenoldopam Mesylate (has salt form). Drug 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. FDA Label 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.

Solubility Data

Solubility (In Vitro)

DMSO: ~77 mg/mL (~251.8 mM) Water: ~10 mg/mL

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2705 mL	16.3527 mL	32.7054 mL
	5 mM	0.6541 mL	3.2705 mL	6.5411 mL
	10 mM	0.3271 mL	1.6353 mL	3.2705 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.