Details of the Drug

General Information of Drug (ID: DMEWC7N)

• Drug Name: Prazepam
• Synonyms: Centrax; Demetrin; Lysanxia; Prazeene; Prazene; Prazepamum; Sedapran; Settima; Trepidan; Verstran; W 4020; Centrac (TN); Centrax (TN); Demetrin (TN); K-373; Lysanxia (TN); Mono Demetrin (TN); Pozapam (TN); Prasepine (TN); Prazene (TN); Prazepamum [INN-Latin]; Reapam (TN); Trepidan (TN); W-4020; Prazepam (JP15/USAN/INN); Prazepam [USAN:INN:BAN:JAN]; 7-Chloro-1-(cyclopropylmethyl)-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one; 7-Chloro-1-(cyclopropylmethyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 7-Chloro-1-cyclopropylmethyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one; 7-chloro-1-(cyclopropylmethyl)-5-phenyl-3H-1,4-benzodiazepin-2-one

Indication

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[1], [2]

• Therapeutic Class: Antianxiety Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 324.8
  Topological Polar Surface Area (xlogp); 3.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Elimination: 0% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 36 - 200 hours [4]
  Metabolism: The drug is metabolized via the hepatic [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.07869 micromolar/kg/day [6]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.004 mg/mL [3]
• Chemical Identifiers:
  Formula: C19H17ClN2O
  IUPAC Name: 7-chloro-1-(cyclopropylmethyl)-5-phenyl-3H-1,4-benzodiazepin-2-one
  Canonical SMILES: C1CC1CN2C(=O)CN=C(C3=C2C=CC(=C3)Cl)C4=CC=CC=C4
  InChI: InChI=1S/C19H17ClN2O/c20-15-8-9-17-16(10-15)19(14-4-2-1-3-5-14)21-11-18(23)22(17)12-13-6-7-13/h1-5,8-10,13H,6-7,11-12H2
  InChIKey: MWQCHHACWWAQLJ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4890
  ChEBI ID: CHEBI:8362
  CAS Number: 2955-38-6
  DrugBank ID: DB01588
  TTD ID: D0G3AQ
  INTEDE ID: DR1328

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Modulator	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[8]

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: 7275).
• [2] Drug information of Prazepam, 2008. eduDrugs.
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] 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.
• [6] 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
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Metabolic profile of oxazepam and related benzodiazepines: clinical and forensic aspects. Drug Metab Rev. 2017 Nov;49(4):451-463.
• [9] 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.
• [10] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [11] 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.
• [12] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [13] 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.
• [14] 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.
• [15] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [16] 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.
• [17] 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.
• [18] Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo. Eur J Pharmacol. 2010 Jan 25;626(2-3):131-8.
• [19] Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46.
• [20] Effects of the combination of metyrapone and oxazepam on cocaine and food self-administration in rats. Pharmacol Biochem Behav. 2008 Nov;91(1):181-9.
• [21] 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. (Target id: 2879).
• [22] Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones. Br J Pharmacol. 1989 Nov;98(3):735-40.
• [23] New hypnotics: perspectives from sleep physiology. Vertex. 2007 Jul-Aug;18(74):294-9.