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

Molecular Formula	C8H11NO3
Molecular Weight	169.1778
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 1950
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 1950
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 1950
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 2014

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
Electrophysiologic studies in the denervated transplanted human heart. II. Response to norepinephrine, isoproterenol and propranolol.	1975 Dec	1106169
Diuresis and improved renal hemodynamics produced by prostaglandin E1 in the dog with norepinephrine-induced acute renal failure.	1975 Jul-Aug	1102487
Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index.	2000 Aug	10972598
Regulation of the human norepinephrine transporter by cocaine and amphetamine.	2000 Dec	11082428
Norepinephrine induces vascular endothelial growth factor gene expression in brown adipocytes through a beta -adrenoreceptor/cAMP/protein kinase A pathway involving Src but independently of Erk1/2.	2000 May 5	10788502
Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture.	2000 Nov	11054474
Near fatal case of atrio-ventricular block induced by amitriptyline at therapeutic dose.	2000 Sep	11089775
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
Effects of brucine, a plant alkaloid, on M(1) muscarinic receptors and alpha(1)-adrenoceptors in the rabbit vas deferens preparation.	2001 Apr	11024498
Plasma catecholamine and cardiovascular responses to physostigmine in Alzheimer's disease and aging.	2001 Feb	11087961
Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization.	2001 Feb 16	11056163
Projections and pathways of VIP- and nNOS-containing airway neurons in ferret trachea.	2001 Jan	11152648
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
Acute gastrointestinal manifestations associated with use of crack.	2001 Jan	11146022
N-methyl-D-aspartate receptors mediating hippocampal noradrenaline and striatal dopamine release display differential sensitivity to quinolinic acid, the HIV-1 envelope protein gp120, external pH and protein kinase C inhibition.	2001 Jan	11145986
Differences in central noradrenergic and behavioural responses of Maudsley non-reactive and Maudsley reactive inbred rats on exposure to an aversive novel environment.	2001 Jan	11145974
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
Efferent arteriole tubuloglomerular feedback in the renal nephron.	2001 Jan	11135074
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
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
The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats.	2001 Jan	11115418
The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting.	2001 Jan	11113036
Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.	2001 Jan	11071707
Neuroendocrine responses to experimentally-induced psychological stress in healthy humans.	2001 Jan	11070337
Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat brain: an autoradiographic study.	2001 Jan	10913689
Loss of noradrenaline transporter sites in frontal cortex of rats with acute (ischemic) liver failure.	2001 Jan	10913685
Characterization of extracellular dopamine clearance in the medial prefrontal cortex: role of monoamine uptake and monoamine oxidase inhibition.	2001 Jan 1	11150317
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
The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat.	2001 Jan 12	11150485
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
Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity.	2001 Mar 16	11092898

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:10:53 GMT 2023` Edited by `admin` on `Fri Dec 15 15:10:53 GMT 2023`
Record UNII	X4W3ENH1CV
Record Status	`Validated (UNII)`
Record Version

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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