Details of the Drug

General Information of Drug (ID: DM78IME)

Drug Name
Ergotidine
Synonyms
Eramin; Ergamine; Histamine; Histaminum; Istamina; Theramine; Free histamine; Histamine Base; Histamine [USAN]; Istamina [Italian]; H7125_SIGMA; [3H]histamine; ALBB-005968; Beta-Aminoethylglyoxaline; Beta-Aminoethylimidazole; Beta-aminothethylglyoxaline; Histamine (DCF); Histamine, Free Base; Histaminum (TN); L-histamine; ZERO/004089; Imidazole-4-ethylamine; Beta-Imidazolyl-4-ethylamine; F411C768-A159-4FC0-A195-291A08BB03AA; 1H-Imidazole-4-ethanamine; 1H-Imidazole-5-ethanamine; 2-(1H-Imidazol-4-yl)ethanamine; 2-(1H-imidazol-4-yl)ethan-1-amine; 2-(1H-imidazol-5-yl)ethanamine; 2-(3H-Imidazol-4-yl)-ethylamine; 2-(4-Imidazolyl)ethylamine; 2-Imidazol-4-ylethylamine; 2-[4-Imidazolyl]ethylamine; 4-(2-Aminoethyl)-1H-imidazole; 4-Imidazoleethylamine; 5-Imidazoleethylamine
Indication
Disease Entry ICD 11 Status REF
Osteoarthritis FA00-FA05 Approved [1]
Respiratory allergy 4A80 Approved [2]
Therapeutic Class
Antiallergic Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 111.15
Logarithm of the Partition Coefficient (xlogp) -0.7
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Absorption
The drug is rapidly absorbed after parenteral administration []
Metabolism
The drug is metabolized via the hepatic []
Chemical Identifiers
Formula
C5H9N3
IUPAC Name
2-(1H-imidazol-5-yl)ethanamine
Canonical SMILES
C1=C(NC=N1)CCN
InChI
InChI=1S/C5H9N3/c6-2-1-5-3-7-4-8-5/h3-4H,1-2,6H2,(H,7,8)
InChIKey
NTYJJOPFIAHURM-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
774
ChEBI ID
CHEBI:18295
CAS Number
51-45-6
DrugBank ID
DB05381
TTD ID
D04USC
VARIDT ID
DR00081
INTEDE ID
DR0810
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Histamine H1 receptor (H1R) TTTIBOJ HRH1_HUMAN Agonist [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Equilibrative nucleoside transporter 4 (SLC29A4) DT3EAQP S29A4_HUMAN Substrate [4]
Vesicular amine transporter 2 (SLC18A2) DTT7VPB VMAT2_HUMAN Substrate [5]
Vesicular amine transporter 1 (SLC18A1) DTM953D VMAT1_HUMAN Substrate [6]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [7]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [9]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Substrate [10]
Histamine N-methyltransferase (HNMT) DE3PZ0I HNMT_HUMAN Substrate [11]
Amiloride-sensitive amine oxidase (AOC1) DETECWH AOC1_HUMAN Substrate [12]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
3',5'-cyclic-AMP phosphodiesterase 4B (PDE4B) OTOA8WU2 PDE4B_HUMAN Gene/Protein Processing [13]
Aquaporin-5 (AQP5) OT77GBY8 AQP5_HUMAN Gene/Protein Processing [14]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Gene/Protein Processing [15]
Beta-glucuronidase (GUSB) OT9N1DK3 BGLR_HUMAN Gene/Protein Processing [16]
Calcium-activated chloride channel regulator 1 (CLCA1) OTL9LPSI CLCA1_HUMAN Gene/Protein Processing [17]
Cyclic AMP-responsive element-binding protein 1 (CREB1) OT1MDLA1 CREB1_HUMAN Post-Translational Modifications [14]
Cytosolic phospholipase A2 (PLA2G4A) OTE70SOT PA24A_HUMAN Gene/Protein Processing [18]
Dicarboxylate carrier SLC25A8 OTA556MK UCP2_HUMAN Regulation of Drug Effects [19]
Equilibrative nucleoside transporter 4 (SLC29A4) OTWTZXMX S29A4_HUMAN Regulation of Drug Effects [20]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Gene/Protein Processing [21]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Osteoarthritis
ICD Disease Classification FA00-FA05
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Histamine H1 receptor (H1R) DTT HRH1 6.74E-01 0.13 0.43
Vesicular amine transporter 2 (SLC18A2) DTP VMAT2 1.35E-03 -2.70E+00 -1.58E+00
Vesicular amine transporter 1 (SLC18A1) DTP VMAT1 2.09E-01 -1.66E-01 -3.68E-01
Organic cation transporter 2 (SLC22A2) DTP SLC22A2 1.57E-01 -2.96E-01 -1.02E+00
Organic cation transporter 3 (SLC22A3) DTP SLC22A3 2.42E-01 2.18E-01 8.46E-01
Equilibrative nucleoside transporter 4 (SLC29A4) DTP ENT4 6.77E-01 7.67E-02 2.27E-01
Amiloride-sensitive amine oxidase (AOC1) DME AOC1 6.20E-01 -8.36E-03 -8.18E-02
Thiopurine methyltransferase (TPMT) DME TPMT 7.06E-01 -1.87E-01 -5.89E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 2.35E-01 2.78E-02 2.09E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.76E-01 1.26E-01 8.27E-01
Histamine N-methyltransferase (HNMT) DME HNMT 6.70E-01 1.08E-01 5.85E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
2 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: 1247).
3 Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
4 Histamine uptake mediated by plasma membrane monoamine transporter and organic cation transporters in rat mast cell lines. Eur J Pharmacol. 2019 Apr 15;849:75-83.
5 The vesicular monoamine transporter 2: an underexplored pharmacological target. Neurochem Int. 2014 Jul;73:89-97.
6 Gastrin-producing endocrine cells: a novel source of histamine in the rat stomach. Endocrinology. 1998 Oct;139(10):4404-15.
7 Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
8 The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11.
9 Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47.
10 Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis. Eur J Neurol. 2010 Feb;17(2):335-8.
11 Histamine pharmacogenomics. Pharmacogenomics. 2009 May;10(5):867-83.
12 Human kidney diamine oxidase: heterologous expression, purification, and characterization. J Biol Inorg Chem. 2002 Jun;7(6):565-79.
13 Histamine up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils. Inflamm Res. 2000 Nov;49(11):600-9. doi: 10.1007/s000110050637.
14 Glycyrrhizin attenuates histamine-mediated MUC5AC upregulation, inflammatory cytokine production, and aquaporin 5 downregulation through suppressing the NF-B pathway in human nasal epithelial cells. Chem Biol Interact. 2018 Apr 1;285:21-26. doi: 10.1016/j.cbi.2018.02.010. Epub 2018 Feb 13.
15 Histamine augments beta2-adrenoceptor-induced cyclic AMP accumulation in human prostate cancer cells DU-145 independently of known histamine receptors. Biochem Pharmacol. 2007 Mar 15;73(6):814-23. doi: 10.1016/j.bcp.2006.11.022. Epub 2006 Dec 1.
16 Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors. J Immunol. 2001 Mar 15;166(6):4083-91.
17 Histamine induces MUC5AC expression via a hCLCA1 pathway. Pharmacology. 2007;80(4):219-26. doi: 10.1159/000104419. Epub 2007 Jul 5.
18 Leukotriene B4 mediates histamine induction of NF-kappaB and IL-8 in human bronchial epithelial cells. Am J Physiol. 1998 Jun;274(6):L1030-9.
19 Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. J Immunol. 2009 Nov 15;183(10):6313-9. doi: 10.4049/jimmunol.0803422. Epub 2009 Oct 21.
20 Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther. 2010 Dec;335(3):743-53. doi: 10.1124/jpet.110.170142. Epub 2010 Sep 21.
21 Human corneal epithelial cell functional responses to inflammatory agents and their antagonists. Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2562-71.