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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

1950
Primary
LEVOPHED

Approved Use

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

Launch Date

1950
Primary
LEVOPHED

Approved Use

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

Launch Date

1950
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

2014
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
Vasopressor agents in shock.
1975 Apr
Electrophysiologic studies in the denervated transplanted human heart. II. Response to norepinephrine, isoproterenol and propranolol.
1975 Dec
Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells.
1999 Apr
Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells.
1999 Jun
Does acute volume overloading in the setting of left ventricular dysfunction and pulmonary hypertension affect the defibrillation threshold?
1999 May
[Distributive shock and it's therapy by cardio-vascular acting drugs].
1999 Oct
[Hypotension refractory to ephedrine after sympathetic blockade in a patient on long-term therapy with tricyclic antidepressants].
1999 Oct
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
Near fatal case of atrio-ventricular block induced by amitriptyline at therapeutic dose.
2000 Sep
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
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
Ventricular activation during sympathetic imbalance and its computational reconstruction.
2001 Jan
Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes.
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
Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.
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
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
IFN-gamma production by Th1 cells generated from naive CD4+ T cells exposed to norepinephrine.
2001 Jan 1
Effect of amlodipine on cardiopulmonary performance in volunteers.
2001 Jan-Feb
Low temperature prevents potentiation of norepinephrine release by phenylephrine.
2001 Mar
Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity.
2001 Mar 16
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 GMT 2023
Edited
by admin
on Sat Dec 16 17:01:18 GMT 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 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
EU-Orphan Drug EU/3/07/465
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
WHO-ATC C01CA27
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
EU-Orphan Drug EU/3/07/466
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
NCI_THESAURUS C38149
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
Code System Code Type Description
USAN
UU-114
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
DRUG CENTRAL
971
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
DAILYMED
J7A92W69L7
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
WIKIPEDIA
L-DOPS
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
MESH
D015103
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
CHEBI
60568
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
NCI_THESAURUS
C73266
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
RXCUI
1489913
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY RxNorm
SMS_ID
100000081029
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
EPA CompTox
DTXSID6046422
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
NDF-RT
N0000178478
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY Increased Blood Pressure [PE]
CAS
23651-95-8
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
IUPHAR
7391
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
FDA UNII
J7A92W69L7
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
ChEMBL
CHEMBL2103827
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
PUBCHEM
92974
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
DRUG BANK
DB06262
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
EVMPD
SUB06420MIG
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
MERCK INDEX
m4774
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY Merck Index
INN
6120
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
CHEBI
31524
Created by admin on Sat Dec 16 17:01:21 GMT 2023 , Edited by admin on Sat Dec 16 17:01:21 GMT 2023
PRIMARY
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Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC