Identification
- Summary
Ketazolam is a long-acting benzodiazepine used to manage anxiety and insomnia.
- Generic Name
- Ketazolam
- DrugBank Accession Number
- DB01587
- Background
Ketazolam is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant activity. Ketazolam is not approved in Canada or America.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Ketazolam (DB01587)
- Weight
- Average: 368.814
Monoisotopic: 368.092770127 - Chemical Formula
- C20H17ClN2O3
- Synonyms
- Ketazolam
- Ketazolamum
- External IDs
- U-28,774
- U-28774
Pharmacology
- Indication
Ketazolam 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Anxiety •••••••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Benzodiazepines 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 action
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.
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Ketazolam is metabolized to diazepam, followed by demoxepam, and finally desmethyldiazepam.
- Route of elimination
Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates.
- Half-life
26-200 hours
- Clearance
Not Available
- Adverse Effects
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Symptoms of overdose include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Ketazolam is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Ketazolam which could result in a higher serum level. Abametapir The serum concentration of Ketazolam can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Ketazolam. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Ketazolam. - Food Interactions
- Avoid alcohol.
- Avoid grapefruit products.
- Limit caffeine intake.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Anseren (Novartis) / Ansieten (Ivax) / Ansietil (Medicamenta Ecuatoriana, Ecuador) / Atenual (Tecnofarma) / Loftran / Marcen (Vegal) / Sedatival F.P. (Recalcine) / Sedavital (Farmindustria) / Sedotime (Faes) / Solatran (GlaxoSmithKline) / Unakalm (Tecnifar)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Loftran Cap 30mg Capsule 30 mg / cap Oral Smithkline Beecham Pharma Division Of Smithkline Beecham Inc 1992-12-31 1996-09-12 Canada 
Categories
- ATC Codes
- N05BA10 — Ketazolam
- Drug Categories
- Anti-Anxiety Agents
- Benzazepines
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Heterocyclic Compounds, Fused-Ring
- Nervous System
- P-glycoprotein substrates
- Psycholeptics
- Psychotropic Drugs
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzodiazepines
- Sub Class
- 1,4-benzodiazepines
- Direct Parent
- 1,4-benzodiazepines
- Alternative Parents
- Alpha amino acids and derivatives / Benzene and substituted derivatives / Aryl chlorides / Vinylogous esters / Tertiary carboxylic acid amides / Lactams / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds show 4 more
- Substituents
- 1,4-benzodiazepine / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 14 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 92A214MD7Y
- CAS number
- 27223-35-4
- InChI Key
- 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[9.4.0.0^{2,7}]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
References
- Synthesis Reference
U.S. Patent 3,575,965.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015526
- PubChem Compound
- 33746
- PubChem Substance
- 46507008
- ChemSpider
- 31110
- 28181
- ChEBI
- 135556
- ChEMBL
- CHEMBL2104356
- PharmGKB
- PA164749385
- Wikipedia
- Ketazolam
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 15 MG Capsule Oral 30 MG Capsule Oral 45 MG Capsule Oral 30 mg / cap - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 174-176 U.S. Patent 3,575,965. - Predicted Properties
Property Value Source Water Solubility 0.0839 mg/mL ALOGPS logP 2.6 ALOGPS logP 3.01 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 14.2 Chemaxon pKa (Strongest Basic) -1.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 49.85 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 99.78 m3·mol-1 Chemaxon Polarizability 36.96 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9965 Blood Brain Barrier + 0.9382 Caco-2 permeable + 0.7069 P-glycoprotein substrate Substrate 0.7006 P-glycoprotein inhibitor I Inhibitor 0.6305 P-glycoprotein inhibitor II Non-inhibitor 0.8837 Renal organic cation transporter Non-inhibitor 0.7534 CYP450 2C9 substrate Non-substrate 0.8193 CYP450 2D6 substrate Non-substrate 0.8504 CYP450 3A4 substrate Substrate 0.7504 CYP450 1A2 substrate Non-inhibitor 0.5878 CYP450 2C9 inhibitor Inhibitor 0.5154 CYP450 2D6 inhibitor Non-inhibitor 0.9257 CYP450 2C19 inhibitor Inhibitor 0.5938 CYP450 3A4 inhibitor Inhibitor 0.6037 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.52 Ames test Non AMES toxic 0.7228 Carcinogenicity Non-carcinogens 0.789 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.8992 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9935 hERG inhibition (predictor II) Non-inhibitor 0.8687
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.6994775 predictedDarkChem Lite v0.1.0 [M-H]- 182.66722 predictedDeepCCS 1.0 (2019) [M+H]+ 185.1329775 predictedDarkChem Lite v0.1.0 [M+H]+ 185.02522 predictedDeepCCS 1.0 (2019) [M+Na]+ 184.9108775 predictedDarkChem Lite v0.1.0 [M+Na]+ 191.73105 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- Curator comments
- The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
- 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...
Components:
References
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- Curator comments
- Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
- 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...
Components:
References
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
Carriers
- Kind
- Protein
- Organism
- Humans
- 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 colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
Transporters
- Kind
- Protein
- Organism
- Humans
- 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
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
Drug created at August 29, 2007 15:28 / Updated at June 12, 2020 16:51