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
SMILES
N[C@@H]([C@H](O)C1=CC=C(O)C(O)=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
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 |
DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203202lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2007/007513Orig1s024lbl.pdfCurator'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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203202lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2007/007513Orig1s024lbl.pdf
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
Norepinephrine (l-arterenol/Levarterenol or l-norepinephrine) is a sympathomimetic catecholamine with multiple roles including as a hormone and a neurotransmitter. As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled. Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle. Norepinephrine can also suppress neuroinflammation when released diffusely in the brain from the locus ceruleus. Norepinephrine may be used for blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion, and drug reactions) and as an adjunct in the treatment of cardiac arrest and profound hypotension. Norepinephrine performs its action by being released into the synaptic cleft, where it acts on adrenergic receptors, followed by the signal termination, either by degradation of norepinephrine, or by uptake by surrounding cells. Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy.If plasma volumes are not corrected, hypotension may recur when Norepinephrine is discontinued, or blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (e.g., decreased renal perfusion)with diminution in blood flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis and possible ischemic injury. Gangrene of extremities has been rarely reported. Overdoses or conventional doses in hypersensitive persons (e.g., hyperthyroid patients) cause severe hypertension with violent headache, photophobia, stabbing retrosternal pain, pallor, intense sweating, and vomiting.
CNS Activity
Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM292631.pdfhttp://www.caam.rice.edu/~cox/wrap/norepinephrine.pdf
Curator's Comment: In the brain, norepinephrine is produced in closely packed brain cell neurons or nuclei that are small yet exert powerful effects on other brain areas.
Originator
Sources: http://www.businesswire.com/news/home/20140218006891/en/Chelsea-Therapeutics-Announces-FDA-Accelerated-Approval-NORTHERA%E2%84%A2Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales (1932), 111, 884-6.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094118 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6124637 |
2600.0 nM [EC50] | ||
Target ID: CHEMBL229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26125514 |
9.1 nM [EC50] | ||
Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25282262 |
128.8 nM [EC50] | ||
Target ID: CHEMBL1942 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18578476 |
61.7 nM [EC50] | ||
Target ID: CHEMBL1916 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18578476 |
794.3 nM [EC50] | ||
Target ID: CHEMBL2331074 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | LEVOPHED Approved UseINDICATIONS: Temporary relief of sleep, emotional, nervous or memory disorders. Launch Date1950 |
|||
Primary | LEVOPHED Approved UseINDICATIONS: Temporary relief of sleep, emotional, nervous or memory disorders. Launch Date1950 |
|||
Primary | LEVOPHED Approved UseINDICATIONS: Temporary relief of sleep, emotional, nervous or memory disorders. Launch Date1950 |
|||
Primary | NORTHERA Approved UseIndicated 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 Date2014 |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.4 min |
unknown, intravenous |
NOREPINEPHRINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
75% |
unknown, intravenous |
NOREPINEPHRINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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 Health Status: unhealthy Age Group: mean 65.5 years Sex: M+F Sources: |
Other AEs: Mean arterial pressure high... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 Health Status: unhealthy Age Group: mean 65.5 years Sex: M+F Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/9848110/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9848110/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9848110/ Page: - |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: - |
yes [Km 10.65 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/ Page: - |
yes [Km 1900 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/26432838/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/27355037/ Page: - |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
The influence of kynurenine, neopterin, and norepinephrine on tubular epithelial cells and alveolar fibroblasts. | 1999 |
|
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 |
|
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 |
|
Inhibition of protein phosphatase 1 induces apoptosis in neonatal rat cardiac myocytes: role of adrenergic receptor stimulation. | 2000 Oct |
|
Near fatal case of atrio-ventricular block induced by amitriptyline at therapeutic dose. | 2000 Sep |
|
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 |
|
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 |
|
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 |
|
Contrasting clinical properties and exercise responses in obese and lean hypertensive patients. | 2001 Jan |
|
Projections and pathways of VIP- and nNOS-containing airway neurons in ferret trachea. | 2001 Jan |
|
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 |
|
Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold. | 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 |
|
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 |
|
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 |
|
Effects of nicotine and cotinine on porcine arterial endothelial cell function. | 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 |
|
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 |
|
Nitric oxide synthase activity in peripheral polymorphonuclear leukocytes in patients with chronic congestive heart failure. | 2001 Jan 15 |
|
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 |
|
A proposed pathological model in the hippocampus of subjects with schizophrenia. | 2001 Jan-Feb |
|
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 |
|
Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity. | 2001 Mar 16 |
|
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
The recommended starting dose is 100 mg, taken orally three times daily: upon arising in the morning, at midday, and in the late afternoon at least 3 hours prior to bedtime (to reduce the potential for supine hypertension during sleep). Administer consistently, either with food or without food. Take capsule whole. Titrate to symptomatic response, in increments of 100 mg three times daily every 2448 hours up to a maximum dose of 600 mg three times daily (i.e., a maximum total daily dose of 1800 mg).
Route of Administration:
Oral
Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 08:41:30 GMT 2025
by
admin
on
Wed Apr 02 08:41:30 GMT 2025
|
Record UNII |
J7A92W69L7
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Preferred Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
229506
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
||
|
EU-Orphan Drug |
EU/3/07/465
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
||
|
WHO-ATC |
C01CA27
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
||
|
EU-Orphan Drug |
EU/3/07/466
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
||
|
NCI_THESAURUS |
C38149
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
UU-114
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
971
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
J7A92W69L7
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
L-DOPS
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
D015103
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
60568
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
C73266
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
1489913
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | RxNorm | ||
|
100000081029
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
DTXSID6046422
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
N0000178478
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | Increased Blood Pressure [PE] | ||
|
23651-95-8
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
7391
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
J7A92W69L7
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
CHEMBL2103827
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
92974
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
DB06262
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
SUB06420MIG
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
m4774
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | Merck Index | ||
|
6120
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
PRIMARY | |||
|
31524
Created by
admin on Wed Apr 02 08:41:31 GMT 2025 , Edited by admin on Wed Apr 02 08:41:31 GMT 2025
|
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 |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE -> PARENT |
|
||
|
METABOLITE -> PARENT |
|
||
|
METABOLITE -> PARENT |
|
||
|
METABOLITE INACTIVE -> PARENT |
|
||
|
METABOLITE -> PARENT |
MAJOR
|
||
|
METABOLITE -> PARENT |
|
||
|
METABOLITE ACTIVE -> PRODRUG |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
IMPURITY -> PARENT |
|
||
|
IMPURITY -> PARENT |
|
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 |
|
|
|||