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Details

Stereochemistry ABSOLUTE
Molecular Formula C8H11NO3.C4H6O6
Molecular Weight 319.2652
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NOREPINEPHRINE BITARTRATE ANHYDROUS

SMILES

c1cc(c(cc1[C@]([H])(CN)O)O)O.[C@@]([H])([C@]([H])(C(=O)O)O)(C(=O)O)O

InChI

InChIKey=WNPNNLQNNJQYFA-YIDNRZKSSA-N
InChI=1S/C8H11NO3.C4H6O6/c9-4-8(12)5-1-2-6(10)7(11)3-5;5-1(3(7)8)2(6)4(9)10/h1-3,8,10-12H,4,9H2;1-2,5-6H,(H,7,8)(H,9,10)/t8-;1-,2-/m01/s1

HIDE SMILES / InChI

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
Involvement of noradrenaline transporters in S-nitrosocysteine-stimulated noradrenaline release from rat brain slices: existence of functional Na(+)-independent transporter activity.
2001 Apr
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.
2001 Apr
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
Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes.
2001 Jan
Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension.
2001 Jan
Contrasting clinical properties and exercise responses in obese and lean hypertensive patients.
2001 Jan
Projections and pathways of VIP- and nNOS-containing airway neurons in ferret trachea.
2001 Jan
Arterial remodeling in chronic sinoaortic-denervated rats.
2001 Jan
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.
2001 Jan
Modulatory effect of protein kinase C activator on contractility of rat vas deferens.
2001 Jan
Hormonal responses to exercise in chronic fatigue syndrome.
2001 Jan
Monoamine compounds in cerebrospinal fluid of healthy subjects punctured without preceding strict bed rest: a pilot study.
2001 Jan
Levels of circulating CD8(+) T lymphocytes, natural killer cells, and eosinophils increase upon acute psychosocial stress in patients with atopic dermatitis.
2001 Jan
Acute gastrointestinal manifestations associated with use of crack.
2001 Jan
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
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
Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest.
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
Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold.
2001 Jan
Ventricular activation during sympathetic imbalance and its computational reconstruction.
2001 Jan
Dorsomedial medulla is more susceptible than rostral ventrolateral medulla to hypoxic insult in cats.
2001 Jan
Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries.
2001 Jan
Catecholamine responses to alpha-adrenergic blockade during exercise in women acutely exposed to altitude.
2001 Jan
Alteration of humoral and peripheral vascular responses during graded exercise in heart failure.
2001 Jan
Effects of PKC isozyme inhibitors on constrictor responses in the feline pulmonary vascular bed.
2001 Jan
Neurotransmitter release from bovine adrenal chromaffin cells is modulated by capacitative Ca(2+)entry driven by depleted internal Ca(2+)stores.
2001 Jan
Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes.
2001 Jan
Catecholaminergic regulation of Na-K-Cl cotransport in pigmented ciliary epithelium: differences between PE and NPE.
2001 Jan
The antidepressant-sensitive dopamine transporter in Drosophila melanogaster: a primordial carrier for catecholamines.
2001 Jan
Neonatal catecholamine levels and neurodevelopmental outcome: a cohort study.
2001 Jan
In vitro reconstitution of fish melanophore pigment aggregation.
2001 Jan
Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion.
2001 Jan
A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue.
2001 Jan
Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release.
2001 Jan
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
Correlation between the release of the sympathetic neurotransmitter ATP and soluble nucleotidases from the guinea pig vas deferens.
2001 Jan
Characterization of extracellular dopamine clearance in the medial prefrontal cortex: role of monoamine uptake and monoamine oxidase inhibition.
2001 Jan 1
Potentiation by aminoethylisothiourea of the extra-cellular Ca(2+) component of norepinephrine-induced contraction in rat femoral arteries.
2001 Jan 1
Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring.
2001 Jan 1
The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat.
2001 Jan 12
Changes in sensitivity of cholinoceptors and adrenoceptors during transhemispheric cortical reorganisation in rat SmI.
2001 Jan 12
Nitric oxide synthase activity in peripheral polymorphonuclear leukocytes in patients with chronic congestive heart failure.
2001 Jan 15
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
A proposed pathological model in the hippocampus of subjects with schizophrenia.
2001 Jan-Feb
Effect of amlodipine on cardiopulmonary performance in volunteers.
2001 Jan-Feb
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.
Name Type Language
NOREPINEPHRINE BITARTRATE ANHYDROUS
Common Name English
NSC-169106
Code English
NOREPINEPHRINE BITARTRATE [WHO-DD]
Common Name English
(2R,3R)-2,3-DIHYDROXYSUCCINIC ACID - 4-((1R)-2-AMINO-1-HYDROXYETHYL)BENZENE-1,2-DIOL
Systematic Name English
NOREPINEPHRINE D-BITARTRATE [MI]
Common Name English
Code System Code Type Description
ECHA (EC/EINECS)
200-095-0
Created by admin on Sat Jun 26 00:45:45 UTC 2021 , Edited by admin on Sat Jun 26 00:45:45 UTC 2021
PRIMARY
CAS
51-40-1
Created by admin on Sat Jun 26 00:45:45 UTC 2021 , Edited by admin on Sat Jun 26 00:45:45 UTC 2021
PRIMARY
PUBCHEM
25127519
Created by admin on Sat Jun 26 00:45:45 UTC 2021 , Edited by admin on Sat Jun 26 00:45:45 UTC 2021
PRIMARY
MERCK INDEX
M8054
Created by admin on Sat Jun 26 00:45:45 UTC 2021 , Edited by admin on Sat Jun 26 00:45:45 UTC 2021
PRIMARY Merck Index
FDA UNII
ZW81GF408B
Created by admin on Sat Jun 26 00:45:45 UTC 2021 , Edited by admin on Sat Jun 26 00:45:45 UTC 2021
PRIMARY