NOREPINEPHRINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H11NO3
Molecular Weight	169.1778
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC[C@H](O)C1=CC(O)=C(O)C=C1

InChI

InChIKey=SFLSHLFXELFNJZ-QMMMGPOBSA-N

InChI=1S/C8H11NO3/c9-4-8(12)5-1-2-6(10)7(11)3-5/h1-3,8,10-12H,4,9H2/t8-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/007513Orig1s024lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203202lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=17214596; http://www.ncbi.nlm.nih.gov/pubmed/?term=18368304

Droxidopa (Northera, Chelsea Therapeutics) is a synthetic catecholamino acid precursor of norepinephrine indicated for the treatment of orthostatic dizziness or lightheadedness in adult patients with symptomatic neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure, dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. Droxidopa was approved as oral therapy in February 2014 under the FDA’s accelerated approval program. Droxidopa is directly metabolized to norepinephrine by dopadecarboxylase. The specific mechanism of action of the drug is not known completely, but it is supposed to exert the pharmacological effects through norepinephrine and not through the parent molecule or other metabolites. It increases blood flow to the brain by stimulating peripheral arterial and venous vasoconstriction.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor beta 87 Target ID: CHEMBL2094118 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6124637	Agonist 2678	2600.0 nM [EC50]
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26125514	Agonist 2678	9.1 nM [EC50]
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25282262	Agonist 2678	128.8 nM [EC50]
Alpha-2b adrenergic receptor 27 Target ID: CHEMBL1942 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18578476	Agonist 2678	61.7 nM [EC50]
Alpha-2c adrenergic receptor 37 Target ID: CHEMBL1916 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18578476	Agonist 2678	794.3 nM [EC50]
Adrenergic receptor 35 Target ID: CHEMBL2331074 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM292631.pdf	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Cardiac arrest 19 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/007513Orig1s024lbl.pdf	Primary	Approved 8429	LEVOPHED Approved Use INDICATIONS: Temporary relief of sleep, emotional, nervous or memory disorders. Launch Date -6.1447681E11
Hypotension 28 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/007513Orig1s024lbl.pdf	Primary	Approved 8429	LEVOPHED Approved Use INDICATIONS: Temporary relief of sleep, emotional, nervous or memory disorders. Launch Date -6.1447681E11
Systemic inflammatory response syndrome 8 Sources: https://clinicaltrials.gov/ct2/show/NCT02755155	Primary	Phase IV 63	LEVOPHED Approved Use INDICATIONS: Temporary relief of sleep, emotional, nervous or memory disorders. Launch Date -6.1447681E11
Neurogenic orthostatic hypotension 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203202lbl.pdf	Primary	Approved 8429	NORTHERA Approved Use Indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure [Parkinson's disease (PD), multiple system atrophy and pure autonomic failure], dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. Launch Date 1.39268155E12

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.4 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/007513s038lbl.pdf	unknown, intravenous		NOREPINEPHRINE unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
75% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/007513s038lbl.pdf	unknown, intravenous		NOREPINEPHRINE unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.6 ug/kg/min single, intravenous Highest studied dose Dose: 0.6 ug/kg/min Route: intravenous Route: single Dose: 0.6 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31490245/	unhealthy, mean 65.5 years n = 85 Health Status: unhealthy Condition: cardiogenic shock Age Group: mean 65.5 years Sex: M+F Population Size: 85 Sources: https://pubmed.ncbi.nlm.nih.gov/31490245/	Other AEs: Mean arterial pressure high... Other AEs: Mean arterial pressure high (7.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/31490245/

AEs

AE	Significance	Dose	Population
Mean arterial pressure high	7.2%	0.6 ug/kg/min single, intravenous Highest studied dose Dose: 0.6 ug/kg/min Route: intravenous Route: single Dose: 0.6 ug/kg/min Sources: https://pubmed.ncbi.nlm.nih.gov/31490245/	unhealthy, mean 65.5 years n = 85 Health Status: unhealthy Condition: cardiogenic shock Age Group: mean 65.5 years Sex: M+F Population Size: 85 Sources: https://pubmed.ncbi.nlm.nih.gov/31490245/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 204 UGT1A3 84 UGT2B7 146	SULT1A3 27 SERT 8 OCT3 80 OCT2 355

Drug as perpetrator

Target	Modality	Activity
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9848110/ Page: -	no
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9848110/ Page: -	no
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9848110/ Page: -	no

Drug as victim

Target	Modality	Activity
SULT1A3 27	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295218300947 Page: -	yes [Km 10.65 uM]
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/ Page: -	yes [Km 1900 uM]
OCT3 80	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26432838/ Page: -	yes
SERT 8	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27355037/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1645	http://www.3bsc.com/index/pro_info.php?id=55364
AA Blocks	AA01BHRG	https://www.aablocks.com/goods/Goods/detail?id=AA01BHRG
AHH Chemical co.,ltd	MT-00064	http://www.ahhchemical.com/product/MT-00064.html
Aaron Chemicals	AR01BIJ8	http://www.aaronchem.com/51-41-2
AbMole Bioscience	M9264	http://www.abmole.com/products/norepinephrine.html
Acadechem	ACDS-063951	http://www.acadechemical.com/product/138650
Achemo Scientific Limited	AC-11490	http://www.achemo.com/product_view.asp?ID=1380
Achemtek	0104-016514	http://www.achemtek.com/51-41-2
Alfa Aesar	L08087	https://www.alfa.com/en/catalog/L08087/
Alfa Chemistry	138-65-8	https://www.alfa-chemistry.com/cas_138-65-8.htm
Anward	ANW-74377	http://www.anward.com/pro_result/60828
Aurum Pharmatech LLC	C-4015	http://www.Aurumpharmatech.com/Product/ProductDetails/C_4015
BioSynth	W-105896	https://www.biosynth.com/en/products/chemical-intermediates/basic-intermediates/products/W-105896.html
Capot Chemical	6074	http://www.capotchem.com/en/6074.htm
Capot Chemical	PubChem6074	http://www.capotchem.com/en/6074.htm
Chem Scene	CS-0007744	http://www.chemscene.com/51-41-2.html
ChemFaces	CFN90047	http://www.chemfaces.com/natural/Norepinephrine-CFN90047.html
Chemenu	CM117224	http://www.chemenu.com/products/CM117224
Chemspace	CSSB00009815836	https://chem-space.com/CSSB00009815836
Clearsynth	CS-O-30989	http://www.clearsynth.com/en/CSO30989.html
Lab Network	LN00142026	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00142026
Matrix Scientific	37592	https://www.matrixscientific.com/037592.html
MedChem Express	HY-13715	https://www.medchemexpress.com/Norepinephrine.html
MuseChem	I008327	https://www.musechem.com/product/I008327.html
OChem	4482	http://www.ocheminc.com/index.php?act=psearch&pid=025N592
Parchem	48632	https://www.parchem.com/chemical-supplier-distributor/L-Noradrenaline-048632.aspx
Selleck Chemicals	S9507	http://www.selleckchem.com/products/norepinephrine.html
Sigma-Aldrich	A7257_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/a7257?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S048294	http://www.sinfoobiotech.com/product/1051692
Smolecule	S537491	http://www.smolecule.com/products/s537491
Smolecule	S752210	https://www.smolecule.com/products/s752210
THE BioTek	bt-277557	https://www.thebiotek.com/product/inhibitors/bt-277557
THE BioTek	bt-299380	https://www.thebiotek.com/product/others/bt-299380
VladaChem	VL274159-1G	https://www.vladachem.com/product.php?products=51-41-2
abcr GmbH	AB178466	http://www.abcr.com/shop/en/AB178466
eNovation Chemicals	D675077	https://www.enovationchem.com/ProductDetails.asp?ProductID=D675077
iChemical	EBD153	http://www.ichemical.com/products/51-41-2.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Involvement of noradrenaline transporters in S-nitrosocysteine-stimulated noradrenaline release from rat brain slices: existence of functional Na(+)-independent transporter activity.	2001 Apr	11137627
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.	2001 Apr	11137626
alpha(1B) adrenergic receptors in gonadotrophin-releasing hormone neurones: relation to Transport-P.	2001 Jan	11156594
Chronic treatment with reboxetine by osmotic pumps facilitates its effect on extracellular noradrenaline and may desensitize alpha(2)-adrenoceptors in the prefrontal cortex.	2001 Jan	11156576
Simvastatin inhibits noradrenaline-induced hypertrophy of cultured neonatal rat cardiomyocytes.	2001 Jan	11156573
Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes.	2001 Jan	11153756
Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension.	2001 Jan	11153742
Contrasting clinical properties and exercise responses in obese and lean hypertensive patients.	2001 Jan	11153733
Projections and pathways of VIP- and nNOS-containing airway neurons in ferret trachea.	2001 Jan	11152648
Arterial remodeling in chronic sinoaortic-denervated rats.	2001 Jan	11152375
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.	2001 Jan	11150921
Modulatory effect of protein kinase C activator on contractility of rat vas deferens.	2001 Jan	11150916
Hormonal responses to exercise in chronic fatigue syndrome.	2001 Jan	11150897
Monoamine compounds in cerebrospinal fluid of healthy subjects punctured without preceding strict bed rest: a pilot study.	2001 Jan	11150891
Levels of circulating CD8(+) T lymphocytes, natural killer cells, and eosinophils increase upon acute psychosocial stress in patients with atopic dermatitis.	2001 Jan	11150008
Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest.	2001 Jan	11136927
Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway.	2001 Jan	11135626
Alteration of catecholamines in pheochromocytoma (PC12) cells in vitro by the metabolites of chlorotriazine herbicide.	2001 Jan	11134552
Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold.	2001 Jan	11133925
Ventricular activation during sympathetic imbalance and its computational reconstruction.	2001 Jan	11133921
Dorsomedial medulla is more susceptible than rostral ventrolateral medulla to hypoxic insult in cats.	2001 Jan	11133917
Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries.	2001 Jan	11133913
Catecholamine responses to alpha-adrenergic blockade during exercise in women acutely exposed to altitude.	2001 Jan	11133901
Alteration of humoral and peripheral vascular responses during graded exercise in heart failure.	2001 Jan	11133893
Effects of PKC isozyme inhibitors on constrictor responses in the feline pulmonary vascular bed.	2001 Jan	11133494
Neurotransmitter release from bovine adrenal chromaffin cells is modulated by capacitative Ca(2+)entry driven by depleted internal Ca(2+)stores.	2001 Jan	11133355
Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes.	2001 Jan	11133229
Catecholaminergic regulation of Na-K-Cl cotransport in pigmented ciliary epithelium: differences between PE and NPE.	2001 Jan	11133177
The antidepressant-sensitive dopamine transporter in Drosophila melanogaster: a primordial carrier for catecholamines.	2001 Jan	11125028
Neonatal catecholamine levels and neurodevelopmental outcome: a cohort study.	2001 Jan	11124926
In vitro reconstitution of fish melanophore pigment aggregation.	2001 Jan	11124706
Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion.	2001 Jan	11124161
A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue.	2001 Jan	11124148
Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release.	2001 Jan	11124136
Chronic type IV phosphodiesterase inhibition protects glomerular filtration rate and renal and mesenteric blood flow in a zymosan-induced model of multiple organ dysfunction syndrome treated with norepinephrine.	2001 Jan	11123377
Correlation between the release of the sympathetic neurotransmitter ATP and soluble nucleotidases from the guinea pig vas deferens.	2001 Jan	11123363
Vagosympathetic interactions in ischemia-induced myocardial norepinephrine and acetylcholine release.	2001 Jan	11123236
Inducible and neuronal nitric oxide synthase involvement in lipopolysaccharide-induced sphincteric dysfunction.	2001 Jan	11123195
Increased alpha(1)- and alpha(2)-adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischemia.	2001 Jan	11121814
Myocardial interstitial norepinephrine and dihydroxyphenylglycol levels during ischemia and reperfusion.	2001 Jan	11121798
Vasoactive intestinal peptide: cardiovascular effects.	2001 Jan	11121793
Chromaffin-adrenocortical cell interactions: effects of chromaffin cell activation in adrenal cell cocultures.	2001 Jan	11121377
Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.	2001 Jan	11120658
Potentiation by aminoethylisothiourea of the extra-cellular Ca(2+) component of norepinephrine-induced contraction in rat femoral arteries.	2001 Jan 1	11137715
Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring.	2001 Jan 1	11136866
Changes in sensitivity of cholinoceptors and adrenoceptors during transhemispheric cortical reorganisation in rat SmI.	2001 Jan 12	11150484
Upregulation of immunoreactive angiotensin II release and angiotensinogen mRNA expression by high-frequency preganglionic stimulation at the canine cardiac sympathetic ganglia.	2001 Jan 19	11139482
Estrogen modulates norepinephrine-induced accumulation of adenosine cyclic monophosphate in a subpopulation of immortalized luteinizing hormone-releasing hormone secreting neurons from the mouse hypothalamus.	2001 Jan 26	11154836
A proposed pathological model in the hippocampus of subjects with schizophrenia.	2001 Jan-Feb	11153541
Effect of amlodipine on cardiopulmonary performance in volunteers.	2001 Jan-Feb	11153533

Patents

Sample Use Guides

In Vivo Use Guide

Acute Hypotension. Initial: 8-12 mcg/min IV infusion; titrate to effect; Maintenance: 2-4 mcg/min IV infusion Cardiac Arrest. Initial: 8-12 mcg/min IV infusion; titrate to effect; Maintenance: 2-4 mcg/min IV infusion

Route of Administration: Intravenous

In Vitro Use Guide

Human umbilical vein endothelial cell line (ECV-304, Shanghai Institute of Cell Biology, Chinese Academy of Science) were used for activity evaluation. Cells were conventionally cultured with modified alpha-MEM containing 10% fetal bovine serum Before all the manipulation experiments, the ECV-304 (VECs) were shifted to serum-free medium (normal medium) and then divided into three groups as follows. Control group was cultured in normal medium in which 0 mol/L NE (Norepinephrine) was detecteded using the NE ELISA kit. NE+Inhibitor group was cultured in normal medium added with 10^-7 mol/L NE (Harcest Pharmaceutical CO,. Shanghai, China) and NE blocker Amitriptyline hydrochloride (10-6 mol/L). NE+Isotype group was cultured in normal medium added with 10^-7 mol/L NE (Norepinephrine) and a negative isotype of NE blocker Amitriptyline hydrochloride. The dose of NE utilized in the experiments was determined in advance through titration. It was selected to approximate the normal concentration in vivo. After 24 h of culture, the supernatant from each group was collected to measure SDF-1 using an ELISA kit (Human CXCL12/SDF-1 alpha Quantikine ELISA Kit; R&D Systems, USA) according to the manufacturer’s protocol. Similarly, the cells from the cell culture were collected for Western blotting analysis. First, proteins were extracted from the cells using the M-PER mammalian protein extraction reagent (Thermo Fisher Scientific, Hudson, USA). Then, the proteins were resolved on a NuPAGE gel and transferred to nylon membranes. After blocking with 7% fat-free dry milk for 2 h, the membranes were incubated with polyclonal rabbit anti-human SDF-1, JNK or p-JNK antibodies (1:200; Santa Cruz) at 4C overnight. After incubation with horseradish peroxidase-conjugated IgG (Santa Cruz) for 1 h, the membranes were treated with chemiluminescent substrate (Thermo) to visualize the protein bands.

Name

Type

Language

NOREPINEPHRINE

Official Name

English

NORADRENALINE

Common Name

English

NORADRENALINE [MART.]

Common Name

English

NOREPINEPHRINE [USP IMPURITY]

Common Name

English

NOREPINEPHRINE [MI]

Common Name

English

(-)-NORADRENALINE

Common Name

English

ADRENALINE IMPURITY B [EP IMPURITY]

Common Name

English

NSC-757246

Code

English

LEVARTERENOL

Common Name

English

(-)-.ALPHA.-(AMINOMETHYL)-3,4-DIHYDROXYBENZYL ALCOHOL

Systematic Name

English

(1R)-2-AMINO-1-(3,4-DIHYDROXYPHENYL)ETHANOL

Systematic Name

English

Norepinephrine [WHO-DD]

Common Name

English

NORADRENALINE [JAN]

Common Name

English

norepinephrine [INN]

Common Name

English

1,2-BENZENEDIOL, 4-(2-AMINO-1-HYDROXYETHYL)-, (R)-(R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE

Common Name

English

NOR ADRENALIN

Brand Name

English

ADRENALINE TARTRATE IMPURITY B [EP IMPURITY]

Common Name

English

NOREPINEPHRINE [HSDB]

Common Name

English

NOREPINEPHRINE [VANDF]

Common Name

English

Classification Tree Code System Code

LOINC

13782-8