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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
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
Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of alpha2-adrenoceptor.
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
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
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
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
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
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
Chromaffin-adrenocortical cell interactions: effects of chromaffin cell activation in adrenal cell cocultures.
2001 Jan
Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring.
2001 Jan 1
Nitric oxide synthase activity in peripheral polymorphonuclear leukocytes in patients with chronic congestive heart failure.
2001 Jan 15
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
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Biological Half-life PHARMACOKINETIC