You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2020-02-26 21:41:46 UTC
HMDB IDHMDB0015526
Secondary Accession Numbers
  • HMDB15526
Metabolite Identification
Common NameKetazolam
DescriptionKetazolam is only found in individuals that have used or taken this drug. It is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Ketazolam is not approved for sale in the United States or Canada. Benzodiazepines share a similar chemical structure and their effects in humans are mainly produced by the allosteric modification of a specific kind of neurotransmitter receptor, the GABAA receptor, which increases the conductance of this inhibitory channel; this results in the various therapeutic effects as well as adverse effects of benzodiazepines. Binding of benzodiazepines to this receptor complex promotes binding of GABA, which in turn increases the conduction of chloride ions across the neuronal cell membrane. This increased conductance raises the membrane potential of the neuron resulting in inhibition of neuronal firing. In addition, different GABAA receptor subtypes have varying distributions within different regions of the brain and therefore control distinct neuronal circuits. Hence, activation of different GABAA receptor subtypes by benzodiazepines may result in distinct pharmacological actions.
Structure
Data?1582753306
Synonyms
ValueSource
MarcenHMDB
SedotimeHMDB
SolatranHMDB
UnakalmHMDB
Chemical FormulaC20H17ClN2O3
Average Molecular Weight368.814
Monoisotopic Molecular Weight368.092770127
IUPAC Name14-chloro-4,10-dimethyl-2-phenyl-3-oxa-7,10-diazatricyclo[9.4.0.0²,⁷]pentadeca-1(11),4,12,14-tetraene-6,9-dione
Traditional Nameketazolam
CAS Registry Number27223-35-4
SMILES
CN1C2=C(C=C(Cl)C=C2)C2(OC(C)=CC(=O)N2CC1=O)C1=CC=CC=C1
InChI Identifier
InChI=1S/C20H17ClN2O3/c1-13-10-18(24)23-12-19(25)22(2)17-9-8-15(21)11-16(17)20(23,26-13)14-6-4-3-5-7-14/h3-11H,12H2,1-2H3
InChI KeyPWAJCNITSBZRBL-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub Class1,4-benzodiazepines
Direct Parent1,4-benzodiazepines
Alternative Parents
Substituents
  • 1,4-benzodiazepine
  • Alpha-amino acid or derivatives
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Vinylogous ester
  • Carboxamide group
  • Lactam
  • Carboxylic acid derivative
  • Oxacycle
  • Azacycle
  • Organochloride
  • Organohalogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.084 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.084 g/LALOGPS
logP2.6ALOGPS
logP3.01ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)14.2ChemAxon
pKa (Strongest Basic)-0.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area49.85 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity99.78 m³·mol⁻¹ChemAxon
Polarizability36.96 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0fri-7794000000-e5f97e7007c42a0e6caeSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-00a0ebc61e31ee5f9fb7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-1009000000-af371ac384c19582e8ccSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00kf-7910000000-9de91642147606a3f899Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009000000-452e71c58ce51c808f39Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0094000000-854abc1e120fa24f40b8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-053v-7293000000-24656d4d8f4834731919Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a59-1290000000-7ef8a75bf466c745a728Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01587 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01587 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01587
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID31110
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkKetazolam
METLIN IDNot Available
PubChem Compound33746
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Signal transduction mechanisms
Specific function:
Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme. Plays a role in the transport of cholesterol across mitochondrial membranes in steroidogenic cells
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular weight:
18778.7
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Falchi AM, Battetta B, Sanna F, Piludu M, Sogos V, Serra M, Melis M, Putzolu M, Diaz G: Intracellular cholesterol changes induced by translocator protein (18 kDa) TSPO/PBR ligands. Neuropharmacology. 2007 Aug;53(2):318-29. Epub 2007 Jun 2. [PubMed:17631921 ]
  3. Vega D, Fernandez D, Echeverria G: Ketazolam. Acta Crystallogr C. 2001 Jul;57(Pt 7):848-50. Epub 2001 Jul 9. [PubMed:11443263 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular weight:
51801.4
References
  1. Blaschke G, Kley H, Muller WE: [Racemation of the benzodiazepines camazepam and ketazolam and receptor binding of enantiomers]. Arzneimittelforschung. 1986 Jun;36(6):893-4. [PubMed:2874815 ]
  2. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090 ]
  3. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456 ]
  4. Derry JM, Dunn SM, Davies M: Identification of a residue in the gamma-aminobutyric acid type A receptor alpha subunit that differentially affects diazepam-sensitive and -insensitive benzodiazepine site binding. J Neurochem. 2004 Mar;88(6):1431-8. [PubMed:15009644 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRB1
Uniprot ID:
P18505
Molecular weight:
54234.1
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090 ]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456 ]
  3. Derry JM, Dunn SM, Davies M: Identification of a residue in the gamma-aminobutyric acid type A receptor alpha subunit that differentially affects diazepam-sensitive and -insensitive benzodiazepine site binding. J Neurochem. 2004 Mar;88(6):1431-8. [PubMed:15009644 ]
  4. Blaschke G, Kley H, Muller WE: [Racemation of the benzodiazepines camazepam and ketazolam and receptor binding of enantiomers]. Arzneimittelforschung. 1986 Jun;36(6):893-4. [PubMed:2874815 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRD
Uniprot ID:
O14764
Molecular weight:
50707.8
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090 ]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRE
Uniprot ID:
P78334
Molecular weight:
57971.2
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090 ]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456 ]
General function:
Involved in ion transport
Specific function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Gene Name:
GABRG1
Uniprot ID:
Q8N1C3
Molecular weight:
53594.5
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090 ]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH, Chiba M, Lin JH: In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther. 2001 Mar;296(3):723-35. [PubMed:11181899 ]
  2. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684 ]