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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H11NO5
Molecular Weight 213.1877
Optical Activity ( - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DROXIDOPA

SMILES

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

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
Increased plasma noradrenaline concentrations in essential hypertension and their decrease after long-term treatment with a beta-receptor-blocking agent (prindolol).
1976 Dec
[Pharmacological studies of antipsychotic drug, penfluridol. 2. General pharmacological properties].
1976 Jul
Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock.
1999 Feb
Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension.
1999 Jul 9
Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells.
1999 Jun
Nitroprusside inhibits thermal hyperalgesia induced by noradrenaline in capsaicin-treated skin.
1999 Mar
[Distributive shock and it's therapy by cardio-vascular acting drugs].
1999 Oct
Characterization of human recombinant alpha(2A)-adrenoceptors expressed in Chinese hamster lung cells using intracellular Ca(2+) changes: evidence for cross-talk between recombinant alpha(2A)- and native alpha(1)-adrenoceptors.
2000 Apr
Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index.
2000 Aug
Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture.
2000 Nov
Near fatal case of atrio-ventricular block induced by amitriptyline at therapeutic dose.
2000 Sep
Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension.
2001 Jan
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.
2001 Jan
Hormonal responses to exercise in chronic fatigue syndrome.
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
Ventricular activation during sympathetic imbalance and its computational reconstruction.
2001 Jan
Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries.
2001 Jan
The antidepressant-sensitive dopamine transporter in Drosophila melanogaster: a primordial carrier for catecholamines.
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
Melatonin potentiates NE-induced vasoconstriction without augmenting cytosolic calcium concentration.
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
The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting.
2001 Jan
Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.
2001 Jan
Loss of noradrenaline transporter sites in frontal cortex of rats with acute (ischemic) liver failure.
2001 Jan
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
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
Upregulation of immunoreactive angiotensin II release and angiotensinogen mRNA expression by high-frequency preganglionic stimulation at the canine cardiac sympathetic ganglia.
2001 Jan 19
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
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
DROXIDOPA [WHO-DD]
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 [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 Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
EU-Orphan Drug EU/3/07/465
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
WHO-ATC C01CA27
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
EU-Orphan Drug EU/3/07/466
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
NCI_THESAURUS C38149
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
Code System Code Type Description
DRUG CENTRAL
971
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
WIKIPEDIA
L-DOPS
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
MESH
D015103
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
NCI_THESAURUS
C73266
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
RXCUI
1489913
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY RxNorm
EPA CompTox
23651-95-8
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
NDF-RT
N0000178478
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY Increased Blood Pressure [PE]
CAS
23651-95-8
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
IUPHAR
7391
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
FDA UNII
J7A92W69L7
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
ChEMBL
CHEMBL2103827
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
PUBCHEM
92974
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
DRUG BANK
DB06262
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
EVMPD
SUB06420MIG
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY
MERCK INDEX
M4774
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY Merck Index
INN
6120
Created by admin on Fri Jun 25 21:21:17 UTC 2021 , Edited by admin on Fri Jun 25 21:21:17 UTC 2021
PRIMARY