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Details

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

SHOW SMILES / InChI
Structure of THREO-DIHYDROXYPHENYLSERINE

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
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
Does acute volume overloading in the setting of left ventricular dysfunction and pulmonary hypertension affect the defibrillation threshold?
1999 May
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
Effects of brucine, a plant alkaloid, on M(1) muscarinic receptors and alpha(1)-adrenoceptors in the rabbit vas deferens preparation.
2001 Apr
Plasma catecholamine and cardiovascular responses to physostigmine in Alzheimer's disease and aging.
2001 Feb
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
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
Arterial remodeling in chronic sinoaortic-denervated rats.
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
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
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
Correlation between the release of the sympathetic neurotransmitter ATP and soluble nucleotidases from the guinea pig vas deferens.
2001 Jan
Increased alpha(1)- and alpha(2)-adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischemia.
2001 Jan
Myocardial interstitial norepinephrine and dihydroxyphenylglycol levels during ischemia and reperfusion.
2001 Jan
Vasoactive intestinal peptide: cardiovascular effects.
2001 Jan
Chromaffin-adrenocortical cell interactions: effects of chromaffin cell activation in adrenal cell cocultures.
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
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
Low temperature prevents potentiation of norepinephrine release by phenylephrine.
2001 Mar
L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.
2006 Fall-Winter
Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats.
2012 Nov
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 Fri Dec 15 15:17:39 GMT 2023
Edited
by admin
on Fri Dec 15 15:17:39 GMT 2023
Record UNII
24A0V01WKS
Record Status Validated (UNII)
Record Version
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Name Type Language
THREO-DIHYDROXYPHENYLSERINE
Common Name English
3,4-DIHYDROXYPHENYLSERINE-THREO, DL-
Common Name English
SERINE, 3-(3,4-DIHYDROXYPHENYL)-, DL-THREO-
Common Name English
DL-THREO-3,4-DIHYDROXYPHENYLSERINE
Common Name English
DL-TYROSINE, .BETA.,3-DIHYDROXY-, THREO-
Common Name English
D-TYROSINE, .BETA.,3-DIHYDROXY-, (.BETA.S)-REL-
Systematic Name English
DL-THREO-DIHYDROXYPHENYLSERINE
Common Name English
DL-THREO-DOPS
Common Name English
Code System Code Type Description
ECHA (EC/EINECS)
223-480-5
Created by admin on Fri Dec 15 15:17:39 GMT 2023 , Edited by admin on Fri Dec 15 15:17:39 GMT 2023
PRIMARY
PUBCHEM
92974
Created by admin on Fri Dec 15 15:17:39 GMT 2023 , Edited by admin on Fri Dec 15 15:17:39 GMT 2023
PRIMARY
CAS
3916-18-5
Created by admin on Fri Dec 15 15:17:39 GMT 2023 , Edited by admin on Fri Dec 15 15:17:39 GMT 2023
PRIMARY
EPA CompTox
DTXSID201017236
Created by admin on Fri Dec 15 15:17:39 GMT 2023 , Edited by admin on Fri Dec 15 15:17:39 GMT 2023
PRIMARY
FDA UNII
24A0V01WKS
Created by admin on Fri Dec 15 15:17:39 GMT 2023 , Edited by admin on Fri Dec 15 15:17:39 GMT 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> RACEMATE