Norepinephrine
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Basic Info
| Common Name | Norepinephrine(F05241) |
| 2D Structure | |
| Description | Noradrenalin is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. |
| FRCD ID | F05241 |
| CAS Number | 51-41-2 |
| PubChem CID | 439260 |
| Formula | C8H11NO3 |
| IUPAC Name | 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol |
| InChI Key | SFLSHLFXELFNJZ-QMMMGPOBSA-N |
| InChI | InChI=1S/C8H11NO3/c9-4-8(12)5-1-2-6(10)7(11)3-5/h1-3,8,10-12H,4,9H2/t8-/m0/s1 |
| Canonical SMILES | C1=CC(=C(C=C1C(CN)O)O)O |
| Isomeric SMILES | C1=CC(=C(C=C1[C@H](CN)O)O)O |
| Wikipedia | Norepinephrine |
| Synonyms |
norepinephrine
L-Norepinephrine
L-Noradrenaline
Levarterenol
Arterenol
noradrenaline
Levophed
(-)-Norepinephrine
51-41-2
(R)-Noradrenaline
|
| Classifies |
Predicted: Illegal Additives
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Phenols |
| Subclass | Benzenediols |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Catechols |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Catechol - 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Aralkylamine - Monocyclic benzene moiety - 1,2-aminoalcohol - Secondary alcohol - Organic nitrogen compound - Aromatic alcohol - Hydrocarbon derivative - Primary amine - Organooxygen compound - Organonitrogen compound - Primary aliphatic amine - Organopnictogen compound - Organic oxygen compound - Amine - Alcohol - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as catechols. These are compounds containing a 1,2-benzenediol moiety. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 169.18 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Complexity | 142 |
| Monoisotopic Mass | 169.074 |
| Exact Mass | 169.074 |
| XLogP | -1.2 |
| Formal Charge | 0 |
| Heavy Atom Count | 12 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.9762 |
| Human Intestinal Absorption | HIA+ | 0.9837 |
| Caco-2 Permeability | Caco2- | 0.7985 |
| P-glycoprotein Substrate | Non-substrate | 0.6046 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9441 |
| Non-inhibitor | 0.9285 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9004 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5805 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8702 |
| CYP450 2D6 Substrate | Non-substrate | 0.8667 |
| CYP450 3A4 Substrate | Non-substrate | 0.7986 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9135 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9675 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9798 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9446 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9209 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8839 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9028 |
| Non-inhibitor | 0.7864 | |
| AMES Toxicity | Non AMES toxic | 0.5053 |
| Carcinogens | Non-carcinogens | 0.8942 |
| Fish Toxicity | Low FHMT | 0.7140 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.6945 |
| Honey Bee Toxicity | Low HBT | 0.5655 |
| Biodegradation | Ready biodegradable | 0.5401 |
| Acute Oral Toxicity | II | 0.4487 |
| Carcinogenicity (Three-class) | Non-required | 0.6152 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.0087 | LogS |
| Caco-2 Permeability | 0.1527 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.2298 | LD50, mol/kg |
| Fish Toxicity | 1.9143 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.7358 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Effects of grazing different ergovaline concentrations on vasoactivity of bovine lateral saphenous vein. | J Anim Sci | 2018 Jun 29 | 29701794 |
| Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer. | Toxins (Basel) | 2018 Jan 30 | 29385697 |
| Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus. | Pharm Biol | 2018 Dec | 29569964 |
| Cold adaptive thermogenesis following consumption of certain pungent spiceprinciples: A validation study. | J Therm Biol | 2017 Feb | 28166943 |
| Ability of higenamine and related compounds to enhance glucose uptake in L6cells. | Bioorg Med Chem | 2017 Dec 15 | 29066136 |
| A standardized Hippophae extract (SBL-1) counters neuronal tissue injuries andchanges in neurotransmitters: implications in radiation protection. | Pharm Biol | 2017 Dec | 28552029 |
| Tranylcypromine in mind (Part I): Review of pharmacology. | Eur Neuropsychopharmacol | 2017 Aug | 28655495 |
| Effects of Jiaotaiwan on depressive-like behavior in mice after lipopolysaccharide administration. | Metab Brain Dis | 2017 Apr | 27796565 |
| Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A. | Mar Drugs | 2016 Nov 9 | 27834847 |
| The Chemistry of Neurodegeneration: Kinetic Data and Their Implications. | Mol Neurobiol | 2016 Jul | 26081152 |
| Dopaminergic drugs in type 2 diabetes and glucose homeostasis. | Pharmacol Res | 2016 Jul | 26748034 |
| Ghrelin receptor regulates adipose tissue inflammation in aging. | Aging (Albany NY) | 2016 Jan | 26837433 |
| Octopaminergic system in the central nervous system of the terrestrial slugLimax. | J Comp Neurol | 2016 Dec 15 | 27187577 |
| Catecholamine-Stimulated Growth of Aeromonas hydrophila Requires the TonB2 EnergyTransduction System but Is Independent of the Amonabactin Siderophore. | Front Cell Infect Microbiol | 2016 Dec 12 | 28018865 |
| Morinda citrifolia leaf enhanced performance by improving angiogenesis,mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses. | Food Chem | 2016 Dec 1 | 27374554 |
| Up-regulation of milk secretion with modified microclimate through manipulatingplasminogen-plasmin system in Murrah buffaloes during hot dry season. | Int J Biometeorol | 2016 Dec | 27174413 |
| Chromium supplementation improved post-stroke brain infarction and hyperglycemia. | Metab Brain Dis | 2016 Apr | 26477944 |
| Dietary Catechols and their Relationship to Microbial Endocrinology. | Adv Exp Med Biol | 2016 | 26589215 |
| The co-occurrence of zinc deficiency and social isolation has the oppositeeffects on mood compared with either condition alone due to changes in thecentral norepinephrine system. | Behav Brain Res | 2015 May 1 | 25680677 |
| Protection against 1,2-di-methylhydrazine-induced systemic oxidative stress andaltered brain neurotransmitter status by probiotic Escherichia coli CFR 16secreting pyrroloquinoline quinone. | Curr Microbiol | 2015 May | 25586077 |
Targets
- General Function:
- G-protein coupled amine receptor activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
- Gene Name:
- DRD1
- Uniprot ID:
- P21728
- Molecular Weight:
- 49292.765 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name:
- DRD2
- Uniprot ID:
- P14416
- Molecular Weight:
- 50618.91 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
- General Function:
- Receptor signaling protein activity
- Specific Function:
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
- Gene Name:
- ADRB1
- Uniprot ID:
- P08588
- Molecular Weight:
- 51322.1 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
- Gene Name:
- ADRB3
- Uniprot ID:
- P13945
- Molecular Weight:
- 43518.615 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Serotonin transmembrane transporter activity
- Specific Function:
- Involved in the transport of biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles of neuroendocrine and endocrine cells.
- Gene Name:
- SLC18A1
- Uniprot ID:
- P54219
- Molecular Weight:
- 56256.71 Da
References
- Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E: Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1996 May 14;93(10):5166-71. [8643547 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
- Gene Name:
- ADRB2
- Uniprot ID:
- P07550
- Molecular Weight:
- 46458.32 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Protein heterodimerization activity
- Specific Function:
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1B
- Uniprot ID:
- P35368
- Molecular Weight:
- 56835.375 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
- Gene Name:
- ADRA2C
- Uniprot ID:
- P18825
- Molecular Weight:
- 49521.585 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Alpha1-adrenergic receptor activity
- Specific Function:
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name:
- ADRA1D
- Uniprot ID:
- P25100
- Molecular Weight:
- 60462.205 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Epinephrine binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
- Gene Name:
- ADRA2B
- Uniprot ID:
- P18089
- Molecular Weight:
- 49565.8 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Vitamin d binding
- Specific Function:
- May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
- Gene Name:
- KL
- Uniprot ID:
- Q9UEF7
- Molecular Weight:
- 116179.815 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
- General Function:
- Superoxide-generating nadph oxidase activity
- Specific Function:
- Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
- Gene Name:
- NOX4
- Uniprot ID:
- Q9NPH5
- Molecular Weight:
- 66930.995 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
- Gene Name:
- SLC22A8
- Uniprot ID:
- Q8TCC7
- Molecular Weight:
- 59855.585 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
- General Function:
- Thioesterase binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
- Gene Name:
- ADRA2A
- Uniprot ID:
- P08913
- Molecular Weight:
- 48956.275 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Monoamine transmembrane transporter activity
- Specific Function:
- Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
- Gene Name:
- SLC18A2
- Uniprot ID:
- Q05940
- Molecular Weight:
- 55712.075 Da
References
- Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E: Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1996 May 14;93(10):5166-71. [8643547 ]
- General Function:
- Receptor binding
- Specific Function:
- Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids.
- Gene Name:
- DAO
- Uniprot ID:
- P14920
- Molecular Weight:
- 39473.75 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
- General Function:
- Protein heterodimerization activity
- Specific Function:
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1A
- Uniprot ID:
- P35348
- Molecular Weight:
- 51486.005 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Phosphatidylinositol binding
- Specific Function:
- Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures.
- Gene Name:
- NISCH
- Uniprot ID:
- Q9Y2I1
- Molecular Weight:
- 166627.105 Da
References
- Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]