Details of the Drug

General Information of Drug (ID: DM8TNX3)

• Drug Name: Etizolam
• Synonyms: Etizolam [INN:JAN]; Etizolamum [INN-Latin]; VMZUTJCNQWMAGF-UHFFFAOYSA-N; Y 7131; Y-7131; etizolam; 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine; 40054-69-1; 6-(o-Chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo(3,4-c)thieno(2,3-e)(1,4)-diazepine; 8-Ethyl-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo(3,4c)thieno(2,3e)-1,4-diazepine; A76XI0HL37; AHR 3219; BRN 0572740; C17H15ClN4S; Depas; NCGC00182031-01; UNII-A76XI0HL37

Indication

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Phase 4	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 342.8
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 2,488.6 mcgh/L [2]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2.83 h [2]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Elimination: The amounts of etizolam excreted was 30% in urine was 70% in feces (in a rat study) [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 3.4 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.16676 micromolar/kg/day [5]
  Vd: The volume of distribution (Vd) of drug is 0.9 +/- 0.2 L/kg [4]
• Chemical Identifiers:
  Formula: C17H15ClN4S
  IUPAC Name: 7-(2-chlorophenyl)-4-ethyl-13-methyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene
  Canonical SMILES: CCC1=CC2=C(S1)N3C(=NN=C3CN=C2C4=CC=CC=C4Cl)C
  InChI: VMZUTJCNQWMAGF-UHFFFAOYSA-N
  InChIKey: 1S/C17H15ClN4S/c1-3-11-8-13-16(12-6-4-5-7-14(12)18)19-9-15-21-20-10(2)22(15)17(13)23-11/h4-8H,3,9H2,1-2H3
• Cross-matching ID:
  PubChem CID: 3307
  ChEBI ID: CHEBI:31583
  CAS Number: 40054-69-1
  DrugBank ID: DB09166
  INTEDE ID: DR0665

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	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[7]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Substrate	[8]

References

• [1] A case of etizolam dependence. Indian J Pharmacol. 2014 Nov-Dec;46(6):655-6.
• [2] Gschwend MH, Guserle R, Erenmemisoglu A, Martin W, Tamur U, Kanzik I, Hincal AA: Pharmacokinetics and bioequivalence study of ranitidine film tablets in healthy male subjects. Arzneimittelforschung. 2007;57(6):315-9. doi: 10.1055/s-0031-1296625.
• [3] BDDCS applied to over 900 drugs
• [4] World Health Organization: Etizolam (INN) Pre-Review Report
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism. Eur J Clin Pharmacol. 2004 Aug;60(6):427-30.
• [7] Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. J Clin Pharm Ther. 2007 Aug;32(4):333-41.
• [8] Etizolam (INN) Pre-Review Report.
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• [21] Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8.
• [22] Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51. Arch Biochem Biophys. 1997 Feb 15;338(2):157-64.
• [23] Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol. 1996 Mar;9(2):365-73.
• [24] CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab Dispos. 2000 Aug;28(8):865-8.
• [25] Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos. 2001 Mar;29(3):242-51.
• [26] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [27] 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.
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