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
Respiratory allergy 4A80 Approved [1], [2], [3]
Therapeutic Class
Antiallergic Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 111.15
Topological Polar Surface Area (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 [4]
Metabolism
The drug is metabolized via the hepatic [4]
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

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 [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Equilibrative nucleoside transporter 4 (SLC29A4) DT3EAQP S29A4_HUMAN Substrate [5]
Vesicular amine transporter 2 (SLC18A2) DTT7VPB VMAT2_HUMAN Substrate [6]
Vesicular amine transporter 1 (SLC18A1) DTM953D VMAT1_HUMAN Substrate [7]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [8]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [10]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [10]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Substrate [11]
Histamine N-methyltransferase (HNMT) DE3PZ0I HNMT_HUMAN Substrate [12]
Amiloride-sensitive amine oxidase (AOC1) DETECWH AOC1_HUMAN Substrate [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Respiratory allergy
ICD Disease Classification 4A80
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 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).
2 Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5 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.
6 The vesicular monoamine transporter 2: an underexplored pharmacological target. Neurochem Int. 2014 Jul;73:89-97.
7 Gastrin-producing endocrine cells: a novel source of histamine in the rat stomach. Endocrinology. 1998 Oct;139(10):4404-15.
8 Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
9 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.
10 Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47.
11 Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis. Eur J Neurol. 2010 Feb;17(2):335-8.
12 Histamine pharmacogenomics. Pharmacogenomics. 2009 May;10(5):867-83.
13 Human kidney diamine oxidase: heterologous expression, purification, and characterization. J Biol Inorg Chem. 2002 Jun;7(6):565-79.
14 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
15 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
16 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
17 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
18 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
19 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
20 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
21 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
22 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
23 Genetics of rheumatoid arthritis. Mayo Clin Proc. 2006 Jan;81(1):94-101.
24 Polymorphism of estrogen metabolism genes and cataract. Med Hypotheses. 2004;63(3):494-7.
25 Influence of estradiol-17 beta and progesterone on catechol-O-methyltransferase and monoamine oxidase activities in uterine artery and myometrium of ovariectomized pigs. Arch Vet Pol. 1993;33(1-2):29-37.
26 The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse. Leukemia. 2010 Apr;24(4):715-20.
27 Ascorbic acid inhibits spinal meningeal catechol-o-methyl transferase in vitro, markedly increasing epinephrine bioavailability. Anesthesiology. 1997 Feb;86(2):405-9.
28 Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia. Drug Metab Dispos. 2002 Oct;30(10):1123-8.
29 Adrenal catecholamines and their metabolism in the vitamin A deficient rat. Ann Nutr Metab. 1983;27(3):220-7.
30 Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):542-548.
31 Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in clinical practice in patients with inflammatory bowel diseases. Acta Gastroenterol Belg. 2010 Jul-Sep;73(3):331-5.
32 Nodular regenerative liver hyperplasia as a complication of azathioprine-containing immunosuppressive treatment for Crohn's disease. Immunopharmacol Immunotoxicol. 2011 Jun;33(2):398-402.
33 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
34 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
35 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
36 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
37 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
38 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
39 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
40 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
41 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
42 Putrescine metabolism and the study of diamine oxidase activity in vivo. Agents Actions. 1981 Apr;11(1-2):20-7.
43 Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
44 Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84.
45 Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
46 Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
47 Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
48 Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
49 A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
50 Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2. Drug Metab Pharmacokinet. 2010;25(4):328-34.
51 Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009 Oct;50(4):1227-40.
52 Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
53 Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem. 2010 Jul;114(1):142-9.
54 Organic cation transporters: physiology, toxicology and special focus on ethidium as a novel substrate. Curr Drug Metab. 2009 Jul;10(6):617-31.
55 Organic cation transporter 3 (Slc22a3) is implicated in salt-intake regulation. J Neurosci. 2004 Mar 17;24(11):2846-51.
56 Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol. 2005 Dec 5;70(12):1851-60.
57 SLC18: Vesicular neurotransmitter transporters for monoamines and acetylcholine. Mol Aspects Med. 2013 Apr-Jun;34(2-3):360-72.
58 Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter. J Med Chem. 2018 Oct 25;61(20):9121-9131.
59 Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66.
60 Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene. Mol Autism. 2014 Aug 13;5:43.
61 Clinical research of Ibudilast on treating the steroid resistant allergic rhinitis. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009 Jan;23(2):63-6.
62 Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008 May;107(1):66-79.
63 Update on prescription and over-the-counter histamine inverse agonists in rhinitis therapy. Curr Allergy Asthma Rep. 2009 Mar;9(2):140-8.
64 Central effects of cinnarizine: restricted use in aircrew. Aviat Space Environ Med. 2002 Jun;73(6):570-4.
65 Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs. 2007 Aug;16(8):1295-305.
66 Influence of epinastine hydrochloride, an H1-receptor antagonist, on the function of mite allergen-pulsed murine bone marrow-derived dendritic cell... Mediators Inflamm. 2009;2009:738038.
67 Examining the tolerability of the non-sedating antihistamine desloratadine: a prescription-event monitoring study in England. Drug Saf. 2009;32(2):169-79.
68 Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20.