U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of NOREPINEPHRINE

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
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

Curator's Comment: Droxidopa, a prodrug, is converted mostly peripherally, but also centrally (as it passes through the blood brain barrier) into norepinephrine (NE).

Originator

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LEVOPHED

Approved Use

INDICATIONS: ​Temporary relief of sleep, emotional, nervous or memory disorders.

Launch Date

-6.1447681E11
Primary
LEVOPHED

Approved Use

INDICATIONS: ​Temporary relief of sleep, emotional, nervous or memory disorders.

Launch Date

-6.1447681E11
Primary
LEVOPHED

Approved Use

INDICATIONS: ​Temporary relief of sleep, emotional, nervous or memory disorders.

Launch Date

-6.1447681E11
Primary
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.4 min
unknown, intravenous
NOREPINEPHRINE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
75%
unknown, intravenous
NOREPINEPHRINE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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:
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:
Other AEs: Mean arterial pressure high...
Other AEs:
Mean arterial pressure high (7.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
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:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Diuresis and improved renal hemodynamics produced by prostaglandin E1 in the dog with norepinephrine-induced acute renal failure.
1975 Jul-Aug
Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells.
1999 Apr
Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension.
1999 Jul 9
alpha2C adrenoceptors inhibit adenylyl cyclase in mouse striatum: potential activation by dopamine.
1999 Jun
Nitroprusside inhibits thermal hyperalgesia induced by noradrenaline in capsaicin-treated skin.
1999 Mar
Does acute volume overloading in the setting of left ventricular dysfunction and pulmonary hypertension affect the defibrillation threshold?
1999 May
Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index.
2000 Aug
Regulation of the human norepinephrine transporter by cocaine and amphetamine.
2000 Dec
Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture.
2000 Nov
Involvement of noradrenaline transporters in S-nitrosocysteine-stimulated noradrenaline release from rat brain slices: existence of functional Na(+)-independent transporter activity.
2001 Apr
Effects of brucine, a plant alkaloid, on M(1) muscarinic receptors and alpha(1)-adrenoceptors in the rabbit vas deferens preparation.
2001 Apr
Plasma catecholamine and cardiovascular responses to physostigmine in Alzheimer's disease and aging.
2001 Feb
alpha(1B) adrenergic receptors in gonadotrophin-releasing hormone neurones: relation to Transport-P.
2001 Jan
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
Simvastatin inhibits noradrenaline-induced hypertrophy of cultured neonatal rat cardiomyocytes.
2001 Jan
Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway.
2001 Jan
Efferent arteriole tubuloglomerular feedback in the renal nephron.
2001 Jan
Alteration of catecholamines in pheochromocytoma (PC12) cells in vitro by the metabolites of chlorotriazine herbicide.
2001 Jan
Dorsomedial medulla is more susceptible than rostral ventrolateral medulla to hypoxic insult in cats.
2001 Jan
In vitro reconstitution of fish melanophore pigment aggregation.
2001 Jan
Correlation between the release of the sympathetic neurotransmitter ATP and soluble nucleotidases from the guinea pig vas deferens.
2001 Jan
Melatonin potentiates NE-induced vasoconstriction without augmenting cytosolic calcium concentration.
2001 Jan
ANG II potentiates mitogenic effect of norepinephrine in vascular muscle cells: role of FGF-2.
2001 Jan
Increased alpha(1)- and alpha(2)-adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischemia.
2001 Jan
Myocardial interstitial norepinephrine and dihydroxyphenylglycol levels during ischemia and reperfusion.
2001 Jan
Vasoactive intestinal peptide: cardiovascular effects.
2001 Jan
Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.
2001 Jan
Vatanidipine hydrochloride: a new long-lasting antihypertensive agent.
2001 Jan
Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.
2001 Jan
Neuroendocrine responses to experimentally-induced psychological stress in healthy humans.
2001 Jan
Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat brain: an autoradiographic study.
2001 Jan
IFN-gamma production by Th1 cells generated from naive CD4+ T cells exposed to norepinephrine.
2001 Jan 1
Changes in sensitivity of cholinoceptors and adrenoceptors during transhemispheric cortical reorganisation in rat SmI.
2001 Jan 12
Upregulation of immunoreactive angiotensin II release and angiotensinogen mRNA expression by high-frequency preganglionic stimulation at the canine cardiac sympathetic ganglia.
2001 Jan 19
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
Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity.
2001 Mar 16
L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.
2006 Fall-Winter
Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats.
2012 Nov
Patents

Sample Use Guides

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
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 Wed Jul 05 22:42:30 UTC 2023
Edited
by admin
on Wed Jul 05 22:42:30 UTC 2023
Record UNII
X4W3ENH1CV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NOREPINEPHRINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
NORADRENALINE
MART.  
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
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 44837-3
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 49552-3
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 14852-8
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
WHO-VATC QC01CA03
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 2666-6
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 27221-1
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 16111-7
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 44341-6
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 24523-3
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 13735-6
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 32549-8
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 2668-2
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
NDF-RT N0000007715
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 25963-0
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 2667-4
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 27977-8
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 14854-4
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
LOINC 14853-6
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
WHO-ATC C01CA03
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
NDF-RT N0000175570
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
Code System Code Type Description
IUPHAR
505
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
ChEMBL
CHEMBL1437
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
FDA UNII
X4W3ENH1CV
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
MESH
D009638
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
EPA CompTox
DTXSID5023378
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
DAILYMED
X4W3ENH1CV
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
CHEBI
33569
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
CHEBI
18357
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
SMS_ID
100000083594
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
EVMPD
SUB09360MIG
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
HSDB
7772
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
WIKIPEDIA
Norepinephrine (medication)
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
NSC
757246
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
INN
33
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
DRUG CENTRAL
1960
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
CAS
51-41-2
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-096-6
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
WIKIPEDIA
NOREPINEPHRINE
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
DRUG BANK
DB00368
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
MERCK INDEX
M8054
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C2321
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
PUBCHEM
439260
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
LACTMED
Norepinephrine
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY
RXCUI
7512
Created by admin on Wed Jul 05 22:42:30 UTC 2023 , Edited by admin on Wed Jul 05 22:42:30 UTC 2023
PRIMARY RxNorm
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