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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H11NO5
Molecular Weight 213.1873
Optical Activity ( - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DROXIDOPA

SMILES

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

InChI

InChIKey=QXWYKJLNLSIPIN-JGVFFNPUSA-N
InChI=1S/C9H11NO5/c10-7(9(14)15)8(13)4-1-2-5(11)6(12)3-4/h1-3,7-8,11-13H,10H2,(H,14,15)/t7-,8+/m0/s1

HIDE SMILES / InChI

Molecular Formula C9H11NO5
Molecular Weight 213.1873
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
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
Electrophysiologic studies in the denervated transplanted human heart. II. Response to norepinephrine, isoproterenol and propranolol.
1975 Dec
Regulation of the human norepinephrine transporter by cocaine and amphetamine.
2000 Dec
Differential remodeling of the left and right heart after norepinephrine treatment in rats: studies on cytokines and collagen.
2000 Feb
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
Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture.
2000 Nov
Inhibition of protein phosphatase 1 induces apoptosis in neonatal rat cardiac myocytes: role of adrenergic receptor stimulation.
2000 Oct
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
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
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
Beta-adrenoceptor stimulation attenuates the hypertrophic effect of alpha-adrenoceptor stimulation in adult rat ventricular cardiomyocytes.
2001 Jan
Modulatory effect of protein kinase C activator on contractility of rat vas deferens.
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
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
Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release.
2001 Jan
Correlation between the release of the sympathetic neurotransmitter ATP and soluble nucleotidases from the guinea pig vas deferens.
2001 Jan
Vagosympathetic interactions in ischemia-induced myocardial norepinephrine and acetylcholine release.
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
Effects of nicotine and cotinine on porcine arterial endothelial cell function.
2001 Jan
Vatanidipine hydrochloride: a new long-lasting antihypertensive agent.
2001 Jan
The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats.
2001 Jan
The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting.
2001 Jan
Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat brain: an autoradiographic study.
2001 Jan
Loss of noradrenaline transporter sites in frontal cortex of rats with acute (ischemic) liver failure.
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
IFN-gamma production by Th1 cells generated from naive CD4+ T cells exposed to norepinephrine.
2001 Jan 1
Diacylglycerol kinase theta is translocated and phosphoinositide 3-kinase-dependently activated by noradrenaline but not angiotensin II in intact small arteries.
2001 Jan 1
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
Effect of amlodipine on cardiopulmonary performance in volunteers.
2001 Jan-Feb
Dialysate dihydroxyphenylglycol as a window for in situ axoplasmic norepinephrine disposition.
2001 Mar
Low temperature prevents potentiation of norepinephrine release by phenylephrine.
2001 Mar
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 Sat Dec 16 17:01:18 UTC 2023
Edited
by admin
on Sat Dec 16 17:01:18 UTC 2023
Record UNII
J7A92W69L7
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DROXIDOPA
DASH   INN   JAN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
droxidopa [INN]
Common Name English
DOPS
Code English
DROXIDOPA [VANDF]
Common Name English
(-)-(2S,3R)-2-AMINO-3-(3,4-DIHYDROXYPHENYL)-3-HYDROXYPROPANOIC ACID
Systematic Name English
DROXIDOPA [MI]
Common Name English
DROXIDOPA [ORANGE BOOK]
Common Name English
L-THREO-DOPS
Common Name English
THREO-3,4-DIHYDROXYPHENYLSERINE, L-
Common Name English
Droxidopa [WHO-DD]
Common Name English
DROXIDOPA [USAN]
Common Name English
L-TYROSINE, .BETA.,3-DIHYDROXY-, (.BETA.R)-
Common Name English
NORTHERA
Brand Name English
L-DOPS
Code English
DROXIDOPA [JAN]
Common Name English
DROXIDOPA [MART.]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 229506
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
EU-Orphan Drug EU/3/07/465
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
WHO-ATC C01CA27
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
EU-Orphan Drug EU/3/07/466
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
NCI_THESAURUS C38149
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
Code System Code Type Description
USAN
UU-114
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
DRUG CENTRAL
971
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
DAILYMED
J7A92W69L7
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
WIKIPEDIA
L-DOPS
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
MESH
D015103
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
CHEBI
60568
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
NCI_THESAURUS
C73266
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
RXCUI
1489913
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY RxNorm
SMS_ID
100000081029
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
EPA CompTox
DTXSID6046422
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
NDF-RT
N0000178478
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY Increased Blood Pressure [PE]
CAS
23651-95-8
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
IUPHAR
7391
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
FDA UNII
J7A92W69L7
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
ChEMBL
CHEMBL2103827
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
PUBCHEM
92974
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
DRUG BANK
DB06262
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
EVMPD
SUB06420MIG
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
MERCK INDEX
m4774
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY Merck Index
INN
6120
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
CHEBI
31524
Created by admin on Sat Dec 16 17:01:21 UTC 2023 , Edited by admin on Sat Dec 16 17:01:21 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> AGONIST
TARGET -> AGONIST
TARGET -> AGONIST
BINDER->LIGAND
BINDING
TARGET -> AGONIST
METABOLIC ENZYME -> SUBSTRATE
RACEMATE -> ENANTIOMER
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> AGONIST
TARGET -> AGONIST
TARGET -> AGONIST
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METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
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METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC