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Identification
Name Norepinephrine
Accession Number DB00368 (APRD01299)
Type small molecule
Groups approved
Description

Precursor 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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Arterenol
L-noradrenaline
L-Norepinephrine
Noradrenaline
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Vasoconstrictor Agents
  • Sympathomimetics
  • Adrenergic alpha-Agonists
CAS number 51-41-2
Weight Average: 169.1778
Monoisotopic: 169.073893223
Chemical Formula C8H11NO3
InChI Key InChIKey=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
Plain Text
IUPAC Name
4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol
SMILES
NC[C@H](O)C1=CC(O)=C(O)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Catecholamines and Derivatives
Substructures
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Benzyl Alcohols and Derivatives
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Amino Alcohols
  • Catecholamines and Derivatives
  • Catechols
  • Phenethylamines
  • Aromatic compounds
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication Mainly used to treat patients in vasodilatory shock states such as septic shock and neurogenic shock and has shown a survival benefit over dopamine. Also used as a vasopressor medication for patients with critical hypotension.
Pharmacodynamics Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance.
Mechanism of action Norepinephrine functions as a peripheral vasoconstrictor by acting on alpha-adrenergic receptors. It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it's activity at the beta-adrenergic receptors.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Norepinephrine
    		Norepinephrine sulfate Details
    Norepinephrine
      		3-Methoxy-4-Hydroxyphenylglycol sulfate Details
      Route of elimination Not Available
      Half life Not Available
      Clearance Not Available
      Toxicity In high dose and especially when it is combined with other vasopressors, it can lead to limb ischemia and limb death.
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      Pharmacoeconomics
      Manufacturers
      • Hospira inc
      Packagers
      Dosage forms
      Form Route Strength
      Insert, extended release Intrauterine
      Liquid Intravenous
      Solution Intravenous
      Tablet Oral
      Prices
      Unit description Cost Unit
      Norepinephrine 4 mg/4 ml amp 2.68 USD ml
      Levophed 1 mg/ml ampul 1.49 USD ml
      Norepinephrine 1 mg/ml vial 0.96 USD ml
      Levophed 1 mg/ml vial 0.48 USD ml
      Norepinephrine-d5w 4 mg/250 ml 0.16 USD ml
      Norepinephrine-ns 4 mg/250 ml 0.16 USD ml
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents Not Available
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 217 dec °C PhysProp
      logP -1.24 HANSCH,C ET AL. (1995)
      pKa 8.58 PERRIN,DD (1965)
      Predicted Properties
      Property Value Source
      water solubility 1.25e+01 g/l ALOGPS
      logP -1.4 ALOGPS
      logP -0.68 ChemAxon
      logS -1.1 ALOGPS
      pKa (strongest acidic) 9.5 ChemAxon
      pKa (strongest basic) 8.85 ChemAxon
      physiological charge 1 ChemAxon
      hydrogen acceptor count 4 ChemAxon
      hydrogen donor count 4 ChemAxon
      polar surface area 86.71 ChemAxon
      rotatable bond count 2 ChemAxon
      refractivity 44.46 ChemAxon
      polarizability 16.96 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference Not Available
      External Links
      Resource Link
      KEGG Drug D00076 Link_out
      KEGG Compound C00547 Link_out
      PubChem Compound 439260 Link_out
      PubChem Substance 46506201 Link_out
      ChemSpider 388394 Link_out
      ChEBI 18357 Link_out
      ChEMBL 18357 Link_out
      Therapeutic Targets Database DNC001034 Link_out
      PharmGKB PA450649 Link_out
      HET LNR Link_out
      RxList http://www.rxlist.com/cgi/generic/norepinephrine.htm Link_out
      Drugs.com http://www.drugs.com/mtm/norepinephrine.html Link_out
      Wikipedia http://en.wikipedia.org/wiki/Norepinephrine Link_out
      ATC Codes
      • C01CA03
      AHFS Codes
      • 12:12.12
      • 68:12.00
      PDB Entries
      FDA label Not Available
      MSDS Not Available
      Interactions
      Drug Interactions
      Drug Interaction
      Amitriptyline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine.
      Amoxapine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of norepinephrine.
      Clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of norepinephrine.
      Desipramine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of norepinephrine.
      Desvenlafaxine Desvenlafaxine may increase the tachycardic and vasopressor effects of norepinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
      Doxepin The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of norepinephrine.
      Entacapone Entacapone increases the effect and toxicity of the sympathomimetic, norepinephrine.
      Guanethidine Norepinephrine may decrease the effect of guanethidine.
      Imipramine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of norepinephrine.
      Isocarboxazid Increased arterial pressure
      Linezolid Possible increase of arterial pressure
      Methyldopa Increased arterial pressure
      Midodrine Increased arterial pressure
      Moclobemide Moclobemide increases the sympathomimetic effect of norepinephrine.
      Nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of norepinephrine.
      Phenelzine Increased arterial pressure
      Rasagiline Increased arterial pressure
      Reserpine Increased arterial pressure
      Trimipramine Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Norepinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
      Venlafaxine Venlafaxine may increase the tachycardic and vasopressor effects of Norepinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
      Food Interactions Not Available
      Targets

      1. Alpha-1A adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      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

      Organism class: human
      UniProt ID: P35348 Link_out
      Gene: ADRA1A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      5. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. Pubmed

      2. Alpha-1B adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

      Organism class: human
      UniProt ID: P35368 Link_out
      Gene: ADRA1B Link_out
      Protein Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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
      6. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. Pubmed
      7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      3. Alpha-1D adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

      Organism class: human
      UniProt ID: P25100 Link_out
      Gene: ADRA1D Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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
      6. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. Pubmed
      7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      4. Alpha-2A adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      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

      Organism class: human
      UniProt ID: P08913 Link_out
      Gene: ADRA2A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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
      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
      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
      8. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      5. Alpha-2B adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      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

      Organism class: human
      UniProt ID: P18089 Link_out
      Gene: ADRA2B Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      4. Vizi ES, Katona I, Freund TF: Evidence for presynaptic cannabinoid CB receptor-mediated inhibition of noradrenaline release in the guinea pig lung. Eur J Pharmacol. 2001 Nov 16;431(2):237-44. Pubmed
      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
      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
      7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      6. Alpha-2C adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

      Organism class: human
      UniProt ID: P18825 Link_out
      Gene: ADRA2C Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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 Apr 4;. Pubmed
      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
      7. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      7. Beta-1 adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      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

      Organism class: human
      UniProt ID: P08588 Link_out
      Gene: ADRB1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
      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
      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
      4. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      8. Beta-2 adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      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

      Organism class: human
      UniProt ID: P07550 Link_out
      Gene: ADRB2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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
      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
      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
      8. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. Pubmed

      9. Beta-3 adrenergic receptor

      Pharmacological action: yes
      Actions: agonist

      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

      Organism class: human
      UniProt ID: P13945 Link_out
      Gene: ADRB3 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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
      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

      10. Phenylalanine-4-hydroxylase

      Pharmacological action: no
      Actions: inhibitor
      Organism class: human
      UniProt ID: P00439 Link_out
      Gene: PAH Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      5. Molinoff PB: The regulation of the noradrenergic neuron. J Psychiatr Res. 1974;11:339-45. Pubmed
      Enzymes

      1. Cytochrome P450 1A2

      Actions: inhibitor

      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

      UniProt ID: P05177 Link_out
      Gene: CYP1A2
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      Transporters

      1. Sodium-dependent noradrenaline transporter

      Actions: substrate

      Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

      UniProt ID: P23975 Link_out
      Gene: SLC6A2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      2. Bonisch H, Bruss M: The norepinephrine transporter in physiology and disease. Handb Exp Pharmacol. 2006;(175):485-524. Pubmed
      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
      4. Gutman DA, Owens MJ: Serotonin and norepinephrine transporter binding profile of SSRIs. Essent Psychopharmacol. 2006;7(1):35-41. Pubmed
      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

      2. Solute carrier family 22 member 2

      Actions: substrate, inhibitor

      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

      UniProt ID: O15244 Link_out
      Gene: SLC22A2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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

      3. Solute carrier family 22 member 3

      Actions: substrate, inhibitor

      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

      UniProt ID: O75751 Link_out
      Gene: SLC22A3 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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

      4. Organic cation/carnitine transporter 2

      Actions: inhibitor

      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

      UniProt ID: O76082 Link_out
      Gene: SLC22A5 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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

      5. Solute carrier family 22 member 1

      Actions: substrate

      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

      UniProt ID: O15245 Link_out
      Gene: SLC22A1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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

      6. POU domain, class 5, transcription factor 1

      Actions: substrate

      Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Forms a trimeric complex with SOX2 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206. Critical for early embryogenesis and for embryonic stem cell pluripotency (By similarity)

      UniProt ID: Q01860 Link_out
      Gene: POU5F1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Zhu HJ, Appel DI, Grundemann D, Markowitz JS: Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem. 2010 Jul;114(1):142-9. Epub 2010 Apr 6. Pubmed
      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19