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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-09-22 19:38:37 UTC
HMDB IDHMDB00216
Secondary Accession NumbersNone
Metabolite Identification
Common NameNorepinephrine
DescriptionPrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
Structure
Thumb
Synonyms
  1. (-)-(R)-Norepinephrine
  2. (-)-alpha-(Aminomethyl)protocatechuyl alcohol
  3. (-)-Arterenol
  4. (-)-Noradrenaline
  5. (-)-Norepinephrine
  6. (R)-(-)-Norepinephrine
  7. (R)-4-(2-Amino-1-hydroxyethyl)-1,2-benzenediol
  8. (R)-Noradrenaline
  9. (R)-Norepinephrine
  10. 4-(2-Amino-1-hydroxyethyl)-1,2-benzenediol
  11. 4-[(1R)-2-Amino-1-hydroxyethyl]-1,2-benzenediol
  12. Adrenor
  13. Aktamin
  14. Arterenol
  15. L-2-Amino-1-(3,4-dihydroxyphenyl)ethanol
  16. L-3,4-Dihydroxyphenylethanolamine
  17. L-alpha-(Aminomethyl)-3,4-dihydroxybenzyl alcohol
  18. L-Arterenol
  19. L-Noradrenaline
  20. L-Norepinephrine
  21. Levarterenol
  22. Levoarterenol
  23. Levonor
  24. Levonoradrenaline
  25. Levonorepinephrine
  26. Levophed
  27. Nor-Epirenan
  28. Noradrenalin
  29. Noradrenaline
  30. Norartrinal
  31. Norepirenamine
  32. Sympathin E
Chemical FormulaC8H11NO3
Average Molecular Weight169.1778
Monoisotopic Molecular Weight169.073893223
IUPAC Name4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol
Traditional Namenorepinephrine
CAS Registry Number51-41-2
SMILES
NC[C@H](O)C1=CC(O)=C(O)C=C1
InChI Identifier
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
InChI KeySFLSHLFXELFNJZ-QMMMGPOBSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Homomonocyclic Compounds
ClassPhenols and Derivatives
Sub ClassBenzenediols
Other Descriptors
  • Adrenalines(KEGG)
  • Aromatic Homomonocyclic Compounds
  • Biogenic amines(KEGG)
  • noradrenaline(ChEBI)
Substituents
  • 1,2 Aminoalcohol
  • 1,2 Diphenol
  • Benzyl Alcohol Derivative
  • Phenethylamine
  • Primary Aliphatic Amine (Alkylamine)
  • Secondary Alcohol
Direct ParentCatecholamines and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Tyrosine metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point145.2 - 146.4 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility849 mg/mLNot Available
LogP-1.24HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility12.5 g/LALOGPS
logP-1.4ALOGPS
logP-0.68ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)9.5ChemAxon
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area86.71ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity44.46ChemAxon
Polarizability16.96ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Adrenal Medulla
  • Bladder
  • Brain
  • Central Nervous System
  • Epidermis
  • Fibroblasts
  • Gonads
  • Heart
  • Intestine
  • Kidney
  • Lymphocyte
  • Muscle
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
Pathways
NameSMPDB LinkKEGG Link
Catecholamine BiosynthesisSMP00012map00350
Tyrosine MetabolismSMP00006map00350
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0070 (0.0034-0.011) uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified0.0016 +/- 0.00012 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.00165 +/- 0.001 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.001 +/- 0.0004 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00112 +/- 6.506e-05 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0001 +/- 0.00002 uMAdult (>18 years old)MaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0014 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.02 (0.0096-0.031) uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.047 +/- 0.0050 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.0185 (0.00342-0.0336) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.0138 (0.0062-0.032) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
    • West Cadwell, N.J...
    • Basel, Switzerlan...
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.001 +/- 0.0013 uMAdult (>18 years old)BothHeat stress details
BloodDetected and Quantified0.004 +/- 0.022 uMAdult (>18 years old)BothPheochromocytoma details
BloodDetected and Quantified0.012 +/- 0.005 uMAdult (>18 years old)Bothuremia details
BloodDetected and Quantified0.0037 +/- 0.00048 uMAdult (>18 years old)BothSubarachnoid hemorrhage details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00005 (0.00003-0.00007) uMAdult (>18 years old)BothHypothyroidism details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00141 +/- 8.872e-05 uMAdult (>18 years old)Not Specifiedborderline hypertensives details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000757 +/- 0.000266 uMAdult (>18 years old)Not SpecifiedCerebral infarction, headache, paresthesia and ununconfirmed suspicion of leucemic infaction or brain metastasis with normal CSF value details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00101 uMAdult (>18 years old)Not SpecifiedCerebral infarction, headache, paresthesia and ununconfirmed suspicion of leucemic infaction or brain metastasis with normal CSF value but renal insufficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00108 uMAdult (>18 years old)Not SpecifiedHaemorrhagic infraction details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00432 uMAdult (>18 years old)Not SpecifiedBacterial meningitis details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00214 uMAdult (>18 years old)Not SpecifiedLeucemic meningiosa details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000745 uMAdult (>18 years old)Not SpecifiedEncephalitis details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0001 +/- 0.00002 uMAdult (>18 years old)BothHypothyroidism details
UrineDetected and Quantified0.084 +/- 0.0068 umol/mmol creatinineAdult (>18 years old)BothExercise details
Associated Disorders and Diseases
Disease References
Subarachnoid hemorrhage
  1. Lambert G, Naredi S, Eden E, Rydenhag B, Friberg P: Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: influence of gender and hydrocephalus. Brain Res Bull. 2002 May;58(1):77-82. Pubmed: 12121816
Heat stress
  1. McMorris T, Swain J, Smith M, Corbett J, Delves S, Sale C, Harris RC, Potter J: Heat stress, plasma concentrations of adrenaline, noradrenaline, 5-hydroxytryptamine and cortisol, mood state and cognitive performance. Int J Psychophysiol. 2006 Aug;61(2):204-15. Epub 2005 Nov 23. Pubmed: 16309771
Hypothyroidism
  1. Sjoberg S, Eriksson M, Nordin C: L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study. Eur J Endocrinol. 1998 Nov;139(5):493-7. Pubmed: 9849813
Pheochromocytoma
  1. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW: Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998 Jun;83(6):2175-85. Pubmed: 9626157
Associated OMIM IDs
DrugBank IDDB00368
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB000895
KNApSAcK IDC00001424
Chemspider ID388394
KEGG Compound IDC00547
BioCyc IDNOREPINEPHRINE
BiGG ID35313
Wikipedia LinkNorepinephrine
NuGOwiki LinkHMDB00216
Metagene LinkHMDB00216
METLIN ID5226
PubChem Compound439260
PDB IDLNR
ChEBI ID18357
References
Synthesis ReferenceGoodall, McC.; Kirshner, Norman. Biosynthesis of adrenaline and norepinephrine by sympathetic nerves and ganglia. Circulation (1958), 17 366-71.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Raw I, Schmidt BJ, Merzel J: Catecholamines and congenital pain insensitivity. Braz J Med Biol Res. 1984;17(3-4):271-9. Pubmed: 6085021
  2. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW: Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998 Jun;83(6):2175-85. Pubmed: 9626157
  3. Engelborghs S, Marescau B, De Deyn PP: Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochem Res. 2003 Aug;28(8):1145-50. Pubmed: 12834252
  4. Panholzer TJ, Beyer J, Lichtwald K: Coupled-column liquid chromatographic analysis of catecholamines, serotonin, and metabolites in human urine. Clin Chem. 1999 Feb;45(2):262-8. Pubmed: 9931050
  5. Sjoberg S, Eriksson M, Nordin C: L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study. Eur J Endocrinol. 1998 Nov;139(5):493-7. Pubmed: 9849813
  6. Eklundh T, Eriksson M, Sjoberg S, Nordin C: Monoamine precursors, transmitters and metabolites in cerebrospinal fluid: a prospective study in healthy male subjects. J Psychiatr Res. 1996 May-Jun;30(3):201-8. Pubmed: 8884658
  7. Kaya M, Moriwaki Y, Ka T, Inokuchi T, Yamamoto A, Takahashi S, Tsutsumi Z, Tsuzita J, Oku Y, Yamamoto T: Plasma concentrations and urinary excretion of purine bases (uric acid, hypoxanthine, and xanthine) and oxypurinol after rigorous exercise. Metabolism. 2006 Jan;55(1):103-7. Pubmed: 16324927
  8. Ahlskog JE, Uitti RJ, Tyce GM, O'Brien JF, Petersen RC, Kokmen E: Plasma catechols and monoamine oxidase metabolites in untreated Parkinson's and Alzheimer's diseases. J Neurol Sci. 1996 Mar;136(1-2):162-8. Pubmed: 8815165
  9. Rajda C, Bencsik K, Fuvesi J, Seres E, Vecsei L, Bergquist J: The norepinephrine level is decreased in the lymphocytes of long-term interferon-beta-treated multiple sclerosis patients. Mult Scler. 2006 Jun;12(3):265-70. Pubmed: 16764338
  10. Takahashi S, Gjessing LR: A fluorometric method combined with thin layer chromatography for the determination of norepinephrine, epinephrine and dopamine in human urine. Clin Chim Acta. 1972 Feb;36(2):369-78. Pubmed: 5008799
  11. Ross HA, van Gurp PJ, Willemsen JJ, Lenders JW, Tack CJ, Sweep FC: Transport within the interstitial space, rather than membrane permeability, determines norepinephrine recovery in microdialysis. J Pharmacol Exp Ther. 2006 Nov;319(2):840-6. Epub 2006 Aug 10. Pubmed: 16902052
  12. Martinsons A, Rudzite V, Bratslavska O, Saulite V: The influence of kynurenine, neopterin, and norepinephrine on tubular epithelial cells and alveolar fibroblasts. Adv Exp Med Biol. 1999;467:347-52. Pubmed: 10721076
  13. Lake CR, Sternberg DE, van Kammen DP, Ballenger JC, Ziegler MG, Post RM, Kopin IJ, Bunney WE: Schizophrenia: elevated cerebrospinal fluid norepinephrine. Science. 1980 Jan 18;207(4428):331-3. Pubmed: 7350667
  14. Fernqvist E, Linde B: Potent mental stress and insulin absorption in normal subjects. Diabetes Care. 1988 Sep;11(8):650-5. Pubmed: 3065003
  15. Pasternak K, Dabrowski W, Wyciszczok T, Korycinska A, Dobija J, Biernacka J, Rzecki Z: The relationship between magnesium, epinephrine and norepinephrine blood concentrations during CABG with normovolemic hemodilution. Magnes Res. 2005 Dec;18(4):245-52. Pubmed: 16548139
  16. Albanese J, Leone M, Garnier F, Bourgoin A, Antonini F, Martin C: Renal effects of norepinephrine in septic and nonseptic patients. Chest. 2004 Aug;126(2):534-9. Pubmed: 15302741
  17. Shibahara J, Goto A, Niki T, Tanaka M, Nakajima J, Fukayama M: Primary pulmonary paraganglioma: report of a functioning case with immunohistochemical and ultrastructural study. Am J Surg Pathol. 2004 Jun;28(6):825-9. Pubmed: 15166677
  18. Wanner A, Horvath G, Brieva JL, Kumar SD, Mendes ES: Nongenomic actions of glucocorticosteroids on the airway vasculature in asthma. Proc Am Thorac Soc. 2004;1(3):235-8. Pubmed: 16113440
  19. Zhu Y, Zhang W, Chen M, Liu N, Guo J: [Study on expression of norepinephrine and dopamine placental tissues of normal pregnancy and pregnancy induced hypertension syndrome] Zhonghua Fu Chan Ke Za Zhi. 2002 Mar;37(3):142-5. Pubmed: 11953080
  20. Pastuszak I, Drake R, Elbein AD. Kidney N-acetylgalactosamine (GalNAc)-1-phosphate kinase, a new pathway of GalNAc activation. J Biol Chem. 1996 Aug 23;271(34):20776-82.

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular weight:
58762.475
Reactions
Norepinephrine + Water + Oxygen → 3,4-Dihydroxymandelaldehyde + Ammonia + Hydrogen peroxidedetails
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular weight:
59681.27
Reactions
Norepinephrine + Water + Oxygen → 3,4-Dihydroxymandelaldehyde + Ammonia + Hydrogen peroxidedetails
General function:
Involved in monooxygenase activity
Specific function:
Conversion of dopamine to noradrenaline.
Gene Name:
DBH
Uniprot ID:
P09172
Molecular weight:
69064.45
Reactions
Dopamine + Ascorbic acid + Oxygen → Norepinephrine + Dehydroascorbic acid + Waterdetails
General function:
Involved in magnesium ion binding
Specific function:
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Gene Name:
COMT
Uniprot ID:
P21964
Molecular weight:
30036.77
Reactions
S-Adenosylmethionine + Norepinephrine → S-Adenosylhomocysteine + Normetanephrinedetails
General function:
Involved in amino acid binding
Specific function:
Not Available
Gene Name:
PAH
Uniprot ID:
P00439
Molecular weight:
51861.565
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Martinez A, Andersson KK, Haavik J, Flatmark T: EPR and 1H-NMR spectroscopic studies on the paramagnetic iron at the active site of phenylalanine hydroxylase and its interaction with substrates and inhibitors. Eur J Biochem. 1991 Jun 15;198(3):675-82. Pubmed: 1646718
  4. Martinez A, Haavik J, Flatmark T: Cooperative homotropic interaction of L-noradrenaline with the catalytic site of phenylalanine 4-monooxygenase. Eur J Biochem. 1990 Oct 5;193(1):211-9. Pubmed: 2226440
  5. Molinoff PB: The regulation of the noradrenergic neuron. J Psychiatr Res. 1974;11:339-45. Pubmed: 4156788
General function:
Involved in methyltransferase activity
Specific function:
Converts noradrenaline to adrenaline.
Gene Name:
PNMT
Uniprot ID:
P11086
Molecular weight:
30854.745
Reactions
S-Adenosylmethionine + Norepinephrine → S-Adenosylhomocysteine + Epinephrinedetails
General function:
Involved in phosphotransferase activity, alcohol group as acceptor
Specific function:
Key enzyme in the regulation of glycerol uptake and metabolism.
Gene Name:
GK
Uniprot ID:
P32189
Molecular weight:
57488.675
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
48956.3
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Nyronen T, Pihlavisto M, Peltonen JM, Hoffren AM, Varis M, Salminen T, Wurster S, Marjamaki A, Kanerva L, Katainen E, Laaksonen L, Savola JM, Scheinin M, Johnson MS: Molecular mechanism for agonist-promoted alpha(2A)-adrenoceptor activation by norepinephrine and epinephrine. Mol Pharmacol. 2001 May;59(5):1343-54. Pubmed: 11306720
  4. MacLennan SJ, Reynen PH, Martin RS, Eglen RM, Martin GR: Characterization of human recombinant alpha(2A)-adrenoceptors expressed in Chinese hamster lung cells using extracellular acidification rate changes. Br J Pharmacol. 2000 Apr;129(7):1333-8. Pubmed: 10742288
  5. Hieble JP, Hehr A, Li YO, Ruffolo RR Jr: Molecular basis for the stereoselective interactions of catecholamines with alpha-adrenoceptors. Proc West Pharmacol Soc. 1998;41:225-8. Pubmed: 9836297
  6. Nash DT: Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. Clin Cardiol. 1990 Nov;13(11):764-72. Pubmed: 1980236
  7. Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. Pubmed: 18680204
  8. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
49953.1
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Gobbi M, Frittoli E, Mennini T: The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain synaptosomes is not mediated by the alpha 2B-adrenoceptor subtype. Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):382-6. Pubmed: 1979424
  4. Vizi ES, Katona I, Freund TF: Evidence for presynaptic cannabinoid CB(1) receptor-mediated inhibition of noradrenaline release in the guinea pig lung. Eur J Pharmacol. 2001 Nov 16;431(2):237-44. Pubmed: 11728431
  5. Rudling JE, Richardson J, Evans PD: A comparison of agonist-specific coupling of cloned human alpha(2)-adrenoceptor subtypes. Br J Pharmacol. 2000 Nov;131(5):933-41. Pubmed: 11053214
  6. Nash DT: Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. Clin Cardiol. 1990 Nov;13(11):764-72. Pubmed: 1980236
  7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in G-protein coupled receptor protein signaling pathway
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
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular weight:
51322.1
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
  2. Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. Pubmed: 9464897
  3. El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. Pubmed: 19110970
  4. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
46458.3
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Sanders VM: The role of norepinephrine and beta-2-adrenergic receptor stimulation in the modulation of Th1, Th2, and B lymphocyte function. Adv Exp Med Biol. 1998;437:269-78. Pubmed: 9666280
  4. Tarizzo VI, Coppes RP, Dahlof C, Zaagsma J: Pre- and postganglionic stimulation-induced noradrenaline overflow is markedly facilitated by a prejunctional beta 2-adrenoceptor-mediated control mechanism in the pithed rat. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jun;349(6):570-7. Pubmed: 7969507
  5. Weinshenker D, Szot P, Miller NS, Palmiter RD: Alpha(1) and beta(2) adrenoreceptor agonists inhibit pentylenetetrazole-induced seizures in mice lacking norepinephrine. J Pharmacol Exp Ther. 2001 Sep;298(3):1042-8. Pubmed: 11504801
  6. Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. Pubmed: 9464897
  7. El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. Pubmed: 19110970
  8. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in G-protein coupled receptor protein signaling pathway
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
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular weight:
51486.0
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Lachnit WG, Tran AM, Clarke DE, Ford AP: Pharmacological characterization of an alpha 1A-adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat. Br J Pharmacol. 1997 Mar;120(5):819-26. Pubmed: 9138687
  4. Burt RP, Chapple CR, Marshall I: The role of diacylglycerol and activation of protein kinase C in alpha 1A-adrenoceptor-mediated contraction to noradrenaline of rat isolated epididymal vas deferens. Br J Pharmacol. 1996 Jan;117(1):224-30. Pubmed: 8825367
  5. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. Pubmed: 17266602
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular weight:
56835.4
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Izzo NJ Jr, Tulenko TN, Colucci WS: Phorbol esters and norepinephrine destabilize alpha 1B-adrenergic receptor mRNA in vascular smooth muscle cells. J Biol Chem. 1994 Jan 21;269(3):1705-10. Pubmed: 8294418
  4. Testa R, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype. Br J Pharmacol. 1995 Feb;114(4):745-50. Pubmed: 7773533
  5. Izzo NJ Jr, Colucci WS: Regulation of alpha 1B-adrenergic receptor half-life: protein synthesis dependence and effect of norepinephrine. Am J Physiol. 1994 Mar;266(3 Pt 1):C771-5. Pubmed: 8166240
  6. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. Pubmed: 17266602
  7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular weight:
60462.2
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Cleary L, Slattery J, Bexis S, Docherty JR: Sympathectomy reveals alpha 1A- and alpha 1D-adrenoceptor components to contractions to noradrenaline in rat vas deferens. Br J Pharmacol. 2004 Nov;143(6):745-52. Epub 2004 Sep 27. Pubmed: 15451776
  4. Kenny BA, Chalmers DH, Philpott PC, Naylor AM: Characterization of an alpha 1D-adrenoceptor mediating the contractile response of rat aorta to noradrenaline. Br J Pharmacol. 1995 Jul;115(6):981-6. Pubmed: 7582530
  5. Testa R, Destefani C, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: The alpha 1d-adrenoceptor subtype is involved in the noradrenaline-induced contractions of rat aorta. Life Sci. 1995;57(13):PL159-63. Pubmed: 7674815
  6. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. Pubmed: 17266602
  7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in transporter activity
Specific function:
May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Regulates the Ca(2+)- dependent secretion of norepinephrine in PC12 cells. Required for export from the endocytic recycling compartment to the cell surface
Gene Name:
SYT5
Uniprot ID:
O00445
Molecular weight:
42900.2
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
43518.6
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Carpene C, Galitzky J, Collon P, Esclapez F, Dauzats M, Lafontan M: Desensitization of beta-1 and beta-2, but not beta-3, adrenoceptor-mediated lipolytic responses of adipocytes after long-term norepinephrine infusion. J Pharmacol Exp Ther. 1993 Apr;265(1):237-47. Pubmed: 8097243
  4. Galitzky J, Carpene C, Lafontan M, Berlan M: [Specific stimulation of adipose tissue adrenergic beta 3 receptors by octopamine]. C R Acad Sci III. 1993;316(5):519-23. Pubmed: 8106131
  5. Tamaoki J, Chiyotani A, Sakai N, Konno K: Stimulation of ciliary motility mediated by atypical beta-adrenoceptor in canine bronchial epithelium. Life Sci. 1993;53(20):1509-15. Pubmed: 8105356
  6. Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. Pubmed: 9464897
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q9Y6W9
Molecular weight:
6248.1
General function:
Involved in G-protein coupled receptor protein signaling pathway
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:
49521.6
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Shreve PE, Toews ML, Bylund DB: Alpha 2A- and alpha 2C-adrenoceptor subtypes are differentially down-regulated by norepinephrine. Eur J Pharmacol. 1991 Jul 12;207(3):275-6. Pubmed: 1654268
  4. Rump LC, Bohmann C, Schaible U, Schollhorn J, Limberger N: Alpha 2C-adrenoceptor-modulated release of noradrenaline in human right atrium. Br J Pharmacol. 1995 Nov;116(6):2617-24. Pubmed: 8590979
  5. Bruck H, Schwerdtfeger T, Toliat M, Leineweber K, Heusch G, Philipp T, Nurnberg P, Brodde OE: Presynaptic alpha-2C adrenoceptor-mediated control of noradrenaline release in humans: genotype- or age-dependent? Clin Pharmacol Ther. 2007 Nov;82(5):525-30. Epub 2007 Apr 4. Pubmed: 17410123
  6. Nash DT: Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. Clin Cardiol. 1990 Nov;13(11):764-72. Pubmed: 1980236
  7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed: 18064417
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q9UQ04
Molecular weight:
5031.7
General function:
Not Available
Specific function:
Not Available
Gene Name:
NET
Uniprot ID:
Q71UR5
Molecular weight:
1998.3

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3
Gene Name:
SLC22A5
Uniprot ID:
O76082
Molecular weight:
62751.1
References
  1. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. Pubmed: 11160873
  2. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. Pubmed: 10454528
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular weight:
69331.42
References
  1. Habecker BA, Willison BD, Shi X, Woodward WR: Chronic depolarization stimulates norepinephrine transporter expression via catecholamines. J Neurochem. 2006 May;97(4):1044-51. Epub 2006 Mar 29. Pubmed: 16573647
  2. Bonisch H, Bruss M: The norepinephrine transporter in physiology and disease. Handb Exp Pharmacol. 2006;(175):485-524. Pubmed: 16722247
  3. Mandela P, Ordway GA: KCl stimulation increases norepinephrine transporter function in PC12 cells. J Neurochem. 2006 Sep;98(5):1521-30. Epub 2006 Jul 31. Pubmed: 16879714
  4. Gutman DA, Owens MJ: Serotonin and norepinephrine transporter binding profile of SSRIs. Essent Psychopharmacol. 2006;7(1):35-41. Pubmed: 16989291
  5. Ksiazek P, Buraczynska K, Buraczynska M: Norepinephrine transporter gene (NET) polymorphism in patients with type 2 diabetes. Kidney Blood Press Res. 2006;29(6):338-43. Epub 2006 Nov 23. Pubmed: 17124432
General function:
Involved in ion transmembrane transporter activity
Specific function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular weight:
61187.4
References
  1. Busch AE, Quester S, Ulzheimer JC, Gorboulev V, Akhoundova A, Waldegger S, Lang F, Koepsell H: Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1. FEBS Lett. 1996 Oct 21;395(2-3):153-6. Pubmed: 8898084
  2. Breidert T, Spitzenberger F, Grundemann D, Schomig E: Catecholamine transport by the organic cation transporter type 1 (OCT1). Br J Pharmacol. 1998 Sep;125(1):218-24. Pubmed: 9776363
General function:
Involved in ion transmembrane transporter activity
Specific function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular weight:
62564.0
References
  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. Pubmed: 12089365
  2. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. Pubmed: 9830022
  3. Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H: Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52. Pubmed: 9687576
  4. Grundemann D, Koster S, Kiefer N, Breidert T, Engelhardt M, Spitzenberger F, Obermuller N, Schomig E: Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem. 1998 Nov 20;273(47):30915-20. Pubmed: 9812985
General function:
Involved in transmembrane transport
Specific function:
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain
Gene Name:
SLC22A3
Uniprot ID:
O75751
Molecular weight:
61279.5
References
  1. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. Pubmed: 9830022
  2. Grundemann D, Schechinger B, Rappold GA, Schomig E: Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51. Pubmed: 10196521