General Information of Drug Combination (ID: DCCG2C2)

Drug Combination Name
Epinephrine Norepinephrine
Indication
Disease Entry Status REF
Shock Phase 4 [1]
Component Drugs Epinephrine   DM3KJBC Norepinephrine   DMOUC09
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Epinephrine
Disease Entry ICD 11 Status REF
Acute asthma CA23 Approved [2]
Allergy 4A80-4A85 Approved [3]
Anaphylaxis N.A. Approved [2]
Bronchiectasis CA24 Approved [2]
Bronchitis CA20 Approved [2]
Periodontitis DA0C Approved [2]
Pulmonary emphysema CA21.Z Approved [2]
Severe asthma CA23 Approved [2]
Asthma CA23 Investigative [2]
Epinephrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Agonist [6]
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Epinephrine Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [8]
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Epinephrine Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [9]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [10]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [11]
Catechol O-methyltransferase (COMT) DEV3T4A COMT_HUMAN Metabolism [12]
Monoamine oxidase type A (MAO-A) DERE4TU AOFA_HUMAN Metabolism [13]
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Epinephrine Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Increases Uptake [14]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [15]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [16]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Activity [17]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Cleavage [18]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Increases Activity [19]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [20]
Alpha-1A adrenergic receptor (ADRA1A) OTUIWCL5 ADA1A_HUMAN Increases Activity [19]
Alpha-1B adrenergic receptor (ADRA1B) OTSAYAFD ADA1B_HUMAN Increases Activity [19]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [20]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases ADR [21]
Equilibrative nucleoside transporter 4 (SLC29A4) OTWTZXMX S29A4_HUMAN Increases Uptake [14]
Alpha-2A adrenergic receptor (ADRA2A) OTZFGOTP ADA2A_HUMAN Increases ADR [21]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Norepinephrine
Disease Entry ICD 11 Status REF
Alopecia ED70 Approved [4]
Bronchiectasis CA24 Approved [4]
Bronchitis CA20 Approved [4]
Chronic fatigue syndrome 8E49 Approved [4]
Depression 6A70-6A7Z Approved [4]
Psychosexual disorder N.A. Approved [4]
Pulmonary emphysema CA21.Z Approved [4]
Pure autonomic failure N.A. Approved [4]
Radiodermatitis N.A. Approved [4]
Sepsis 1G40-1G41 Approved [5]
Severe asthma CA23 Approved [4]
Asthma CA23 Investigative [4]
Norepinephrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Stimulator [23]
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Norepinephrine Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [7]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [24]
Vesicular amine transporter 2 (SLC18A2) DTT7VPB VMAT2_HUMAN Substrate [25]
Vesicular amine transporter 1 (SLC18A1) DTM953D VMAT1_HUMAN Substrate [25]
Sodium-dependent noradrenaline transporter (SLC6A2) DT9JBVI SC6A2_HUMAN Substrate [26]
Sodium- and chloride-dependent glycine transporter 2 (SLC6A5) DTE8R17 SC6A5_HUMAN Substrate [27]
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⏷ Show the Full List of 7 DTP(s)
Norepinephrine Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 3 (SLC22A3) OTQYGVXX S22A3_HUMAN Increases Uptake [14]
Protein phosphatase 1 regulatory subunit 12A (PPP1R12A) OT4AVU95 MYPT1_HUMAN Increases Phosphorylation [28]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [29]
Protein S100-B (S100B) OTHHDS33 S100B_HUMAN Increases Expression [30]
Protein S100-A8 (S100A8) OTVMOB3F S10A8_HUMAN Increases Expression [31]
Myosin light chain 1/3, skeletal muscle isoform (MYL1) OTDUYR4U MYL1_HUMAN Increases Phosphorylation [28]
Protein S100-A9 (S100A9) OTOARHCS S10A9_HUMAN Increases Expression [31]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Affects Binding [32]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Increases Secretion [33]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Affects Localization [29]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Affects Binding [34]
Alpha-1A adrenergic receptor (ADRA1A) OTUIWCL5 ADA1A_HUMAN Affects Binding [35]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [29]
Sodium-dependent dopamine transporter (SLC6A3) OT39XG28 SC6A3_HUMAN Increases Uptake [36]
Pro-neuropeptide Y (NPY) OT4ICV3P NPY_HUMAN Affects Response To Substance [37]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Abundance [38]
Equilibrative nucleoside transporter 4 (SLC29A4) OTWTZXMX S29A4_HUMAN Increases Uptake [14]
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⏷ Show the Full List of 17 DOT(s)

References

1 ClinicalTrials.gov (NCT02118467) Vasoactive Drugs in Intensive Care Unit
2 Epinephrine FDA Label
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 509).
4 Norepinephrine FDA Label
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 505).
6 Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: involvement of beta1- and beta2-adrenergic receptors. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G269-77.
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10 Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate. Biochem Biophys Res Commun. 2005 Sep 23;335(2):417-23.
11 Adrenal catecholamines and their metabolism in the vitamin A deficient rat. Ann Nutr Metab. 1983;27(3):220-7.
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13 Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study. J Neurooncol. 2019 Nov;145(2):287-294.
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19 Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
20 Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway. Cardiovasc Res. 2000 Feb;45(3):788-94. doi: 10.1016/s0008-6363(99)00369-7.
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22 Vitamin D signaling and the differentiation of developing dopamine systems. Neuroscience. 2016 Oct 1;333:193-203. doi: 10.1016/j.neuroscience.2016.07.020. Epub 2016 Jul 20.
23 Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999 Feb;27(2):325-31.
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26 Chronic depolarization stimulates norepinephrine transporter expression via catecholamines. J Neurochem. 2006 May;97(4):1044-51.
27 SLC6A2 Gene (Protein Coding).
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30 Inhibition of norepinephrine-induced cardiac hypertrophy in s100beta transgenic mice. J Clin Invest. 1998 Oct 15;102(8):1609-16. doi: 10.1172/JCI3077.
31 Norepinephrine stimulates calprotectin expression in human monocytic cells. J Periodontal Res. 2006 Jun;41(3):159-64. doi: 10.1111/j.1600-0765.2005.00845.x.
32 Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking ?-adrenergic signaling. Arch Biochem Biophys. 2014 Sep 1;557:18-27. doi: 10.1016/j.abb.2014.05.030. Epub 2014 Jun 11.
33 Norepinephrine induces calcium spikes and proinflammatory actions in human hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2006 Nov;291(5):G877-84. doi: 10.1152/ajpgi.00537.2005. Epub 2006 Jun 15.
34 Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane. Sci China C Life Sci. 2004 Aug;47(4):376-81. doi: 10.1360/03yc0109.
35 The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8.
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37 Release and functional role of neuropeptide Y as a sympathetic modulator in human saphenous vein biopsies. Peptides. 2004 Jan;25(1):53-64. doi: 10.1016/j.peptides.2003.11.001.
38 Nesiritide: past, present, and future. Minerva Cardioangiol. 2005 Dec;53(6):509-22.