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Identification
NameKetazolam
Accession NumberDB01587
TypeSmall Molecule
GroupsApproved
Description

Ketazolam 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.

Structure
Thumb
Synonyms
Ketazolam
U-28774
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Loftran Cap 30mgcapsule30 mgoralSmithkline Beecham Pharma Division Of Smithkline Beecham Inc1992-12-311996-09-12Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AnserenNovartis
AnsietenIvax
AnsietilMedicamenta Ecuatoriana, Ecuador
AtenualTecnofarma
MarcenVegal
Sedatival F.P.Recalcine
SedavitalFarmindustria
SedotimeFaes
SolatranGlaxoSmithKline
UnakalmTecnifar
Brand mixturesNot Available
SaltsNot Available
Categories
UNII92A214MD7Y
CAS number27223-35-4
WeightAverage: 368.814
Monoisotopic: 368.092770127
Chemical FormulaC20H17ClN2O3
InChI KeyInChIKey=PWAJCNITSBZRBL-UHFFFAOYSA-N
InChI
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
IUPAC Name
14-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
SMILES
CN1C2=C(C=C(Cl)C=C2)C2(OC(C)=CC(=O)N2CC1=O)C1=CC=CC=C1
Taxonomy
DescriptionThis compound 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
  • Chlorobenzene
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Vinylogous ester
  • Tertiary carboxylic acid amide
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationKetazolam could be used for the treatment of anxiety. In approved countries, it is indicated for the treatment of anxiety, tension, irritability and similar stress related symptoms.
PharmacodynamicsBenzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA), which results in sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant and amnesic action. Benzodiazepines bind nonspecifically to benzodiazepine receptors which mediate sleep, affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
Mechanism of actionBenzodiazepines 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Ketazolam breaks down in the blood to diazepam which breaks down to demoxepam which breaks down to desmethyldiazepam.

Route of eliminationDiazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates.
Half life26-200 hours
ClearanceNot Available
ToxicitySymptoms of overdose include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9965
Blood Brain Barrier+0.9382
Caco-2 permeable+0.7069
P-glycoprotein substrateSubstrate0.7006
P-glycoprotein inhibitor IInhibitor0.6305
P-glycoprotein inhibitor IINon-inhibitor0.8837
Renal organic cation transporterNon-inhibitor0.7534
CYP450 2C9 substrateNon-substrate0.8193
CYP450 2D6 substrateNon-substrate0.8504
CYP450 3A4 substrateSubstrate0.7504
CYP450 1A2 substrateNon-inhibitor0.5878
CYP450 2C9 inhibitorInhibitor0.5154
CYP450 2D6 inhibitorNon-inhibitor0.9257
CYP450 2C19 inhibitorInhibitor0.5938
CYP450 3A4 inhibitorInhibitor0.6037
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.52
Ames testNon AMES toxic0.7228
CarcinogenicityNon-carcinogens0.789
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8992 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9935
hERG inhibition (predictor II)Non-inhibitor0.8687
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral30 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point174-176U.S. Patent 3,575,965.
Predicted Properties
PropertyValueSource
Water Solubility0.0839 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity99.78 m3·mol-1ChemAxon
Polarizability36.96 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0a59-1290000000-7ef8a75bf466c745a728View in MoNA
References
Synthesis Reference

U.S. Patent 3,575,965.

General ReferencesNot Available
External Links
ATC CodesN05BA10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AminophyllineThe therapeutic efficacy of Ketazolam can be decreased when used in combination with Aminophylline.
ClozapineThe risk or severity of adverse effects can be increased when Ketazolam is combined with Clozapine.
DyphyllineThe therapeutic efficacy of Ketazolam can be decreased when used in combination with Dyphylline.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Ketazolam.
Gamma Hydroxybutyric AcidKetazolam may increase the central nervous system depressant (CNS depressant) activities of Gamma Hydroxybutyric Acid.
MethadoneKetazolam may increase the central nervous system depressant (CNS depressant) activities of Methadone.
OlanzapineThe risk or severity of adverse effects can be increased when Olanzapine is combined with Ketazolam.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Ketazolam.
Sodium oxybateKetazolam may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
TeduglutideThe serum concentration of Ketazolam can be increased when it is combined with Teduglutide.
TheophyllineThe therapeutic efficacy of Ketazolam can be decreased when used in combination with Theophylline.
Food Interactions
  • Avoid alcohol
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Avoid taking with grapefruit or grapefruit juice as grapefruit can significantly increase serum levels of this product.
  • Take with food.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benz...
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By si...
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By si...
Gene Name:
GABRB1
Uniprot ID:
P18505
Molecular Weight:
54234.085 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Inhibitory extracellular ligand-gated ion channel activity
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:
53594.49 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Gaba-a receptor activity
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:
50707.835 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Inhibitory extracellular ligand-gated ion channel activity
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:
57971.175 Da
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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase 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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality. 1997;9(4):335-40. [PubMed:9275312 ]
  2. Brodersen R, Honore B: Drug binding properties of neonatal albumin. Acta Paediatr Scand. 1989 May;78(3):342-6. [PubMed:2545072 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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 ]
Comments
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Drug created on August 29, 2007 09:28 / Updated on May 05, 2014 10:10