Details of the Drug

General Information of Drug (ID: DMZKABS)

• Drug Name: Imipramine oxide
• Synonyms: Elepsin; Imipramine N-oxide; Imipramine oxide; Imipraminoxide; Imipraminoxide (INN); Imipraminoxide [INN]; Imipraminoxido; Imipraminoxidum; 5-(3-(Dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine 5-oxide; 5-[3-(Dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine N-oxide; 5H-Dibenz(b,f)azepine-5-propanamine, 10,11-dihydro-N,N-dimethyl-, N-oxide; 5H-Dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N,N-dimethyl-, N-oxide; 6829-98-7; 8MKS280XJW; UNII-8MKS280XJW

Indication

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Investigative	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 296.4
  Topological Polar Surface Area (xlogp); 4.8
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 12 mL/min/kg [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.8 hours [2]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.9 L/kg [2]
• Chemical Identifiers:
  Formula: C19H24N2O
  IUPAC Name: 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine oxide
  Canonical SMILES: C[N+](C)(CCCN1C2=CC=CC=C2CCC3=CC=CC=C31)[O-]
  InChI: QZIQORUGXBPDSU-UHFFFAOYSA-N
  InChIKey: 1S/C19H24N2O/c1-21(2,22)15-7-14-20-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)20/h3-6,8-11H,7,12-15H2,1-2H3
• Cross-matching ID:
  PubChem CID: 65589
  ChEBI ID: CHEBI:135256
  CAS Number: 6829-98-7
  DrugBank ID: DB13782
  INTEDE ID: DR0862

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[3]

References

• [1] National Center for Advancing Translational Science-Inxight: drug (8MKS280XJW)
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol. 1993 May;43(5):827-32.
• [4] 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.
• [5] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [6] 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.
• [7] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [8] 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.
• [9] 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.
• [10] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [11] 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.
• [12] 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.
• [13] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [14] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [15] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [16] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [17] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [18] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [19] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [20] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [21] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.