Identification
- Summary
Clotiazepam is a thienodiazepine used to manage anxiety disorders and insomnia.
- Generic Name
- Clotiazepam
- DrugBank Accession Number
- DB01559
- Background
Clotiazepam is a thienodiazepine, not approved for sale in the U.S. or Canada, but has been approved in the U.K. It is a schedule IV drug in Canada.
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
Structure for Clotiazepam (DB01559)
- Weight
- Average: 318.821
Monoisotopic: 318.059361509 - Chemical Formula
- C16H15ClN2OS
- Synonyms
- Clotiazepam
- Clotiazepamum
- External IDs
- Y 6047
Pharmacology
- Indication
For the treatment of anxiety disorders.
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
- 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
Clotiazepam is a thienodiazepine possessing anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It increases the stage 2 non-rapid eye movement sleep.
- Mechanism of action
Clotiazepam acts at the benzodiazepine receptors (BZD). This agonizes the action of GABA, increasing the frequency of opening of the channel chlorinates and penetration of the ions chlorinates through the ionophore. Increase in membrane polarization decreases the probability of discharge of neurons.
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
99% bound to plasma proteins.
- Metabolism
Hepatic.
- Route of elimination
Not Available
- Half-life
4 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- 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 Clotiazepam is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Clotiazepam can be increased when it is combined with Abametapir. Abatacept The metabolism of Clotiazepam can be increased when combined with Abatacept. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Clotiazepam. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Clotiazepam. - Food Interactions
- Not Available
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
- Clozan (Pfizer) / Distensan (Esteve) / Rize (Dae Woong) / Rizen (Formenti) / Tienor (Farmaka)
Categories
- ATC Codes
- N05BA21 — Clotiazepam
- Drug Categories
- Anti-Anxiety Agents
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Depressants
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Nervous System
- Psycholeptics
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as thienodiazepines. These are heteropolycyclic containing a thiophene ring fused to a diazepine ring. Thiophene is 5-membered ring consisting of four carbon and one sulfur atoms. Diazepine is a 7-membered ring consisting of five carbon and two nitrogen atoms.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thienodiazepines
- Sub Class
- Not Available
- Direct Parent
- Thienodiazepines
- Alternative Parents
- Alpha amino acids and derivatives / 2,3,5-trisubstituted thiophenes / 1,4-diazepines / Chlorobenzenes / Aryl chlorides / Tertiary carboxylic acid amides / Heteroaromatic compounds / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds show 6 more
- Substituents
- 2,3,5-trisubstituted thiophene / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- ZCN055599V
- CAS number
- 33671-46-4
- InChI Key
- CHBRHODLKOZEPZ-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3
- IUPAC Name
- 5-(2-chlorophenyl)-7-ethyl-1-methyl-1H,2H,3H-thieno[2,3-e][1,4]diazepin-2-one
- SMILES
- CCC1=CC2=C(S1)N(C)C(=O)CN=C2C1=CC=CC=C1Cl
References
- Synthesis Reference
Nakanishi, M., Araki, K.,Tahara, T. and Shiroki, M.; US. Patent 3,849,405; November 19, 1974; assigned to Yoshitomi Pharmaceutical Industries, Ltd.
- General References
- Nakazawa Y, Kotorii M, Oshima M, Horikawa S, Tachibana H: Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives. Psychopharmacologia. 1975 Oct 31;44(2):165-71. [Article]
- External Links
- Human Metabolome Database
- HMDB0015512
- KEGG Drug
- D01328
- PubChem Compound
- 2811
- PubChem Substance
- 46508776
- ChemSpider
- 2709
- 2622
- ChEBI
- 31425
- ChEMBL
- CHEMBL1697737
- ZINC
- ZINC000000001207
- Therapeutic Targets Database
- DAP000932
- PharmGKB
- PA164752437
- Wikipedia
- Clotiazepam
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 1 Completed Other Bioequivalence 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution / drops Oral 10 MG/ML Tablet 10 MG Tablet 5 MG - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 105-106 Nakanishi, M., Araki, K.,Tahara, T. and Shiroki, M.; US. Patent 3,849,405; November 19, 1974; assigned to Yoshitomi Pharmaceutical Industries, Ltd. logP 3.18 MARUYAMA,T ET AL. (1992) - Predicted Properties
Property Value Source Water Solubility 0.00537 mg/mL ALOGPS logP 3.58 ALOGPS logP 4.11 Chemaxon logS -4.8 ALOGPS pKa (Strongest Basic) 2.39 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 32.67 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 85.66 m3·mol-1 Chemaxon Polarizability 33.01 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9849 Blood Brain Barrier + 0.97 Caco-2 permeable + 0.662 P-glycoprotein substrate Substrate 0.6147 P-glycoprotein inhibitor I Non-inhibitor 0.7404 P-glycoprotein inhibitor II Non-inhibitor 0.7762 Renal organic cation transporter Non-inhibitor 0.5527 CYP450 2C9 substrate Non-substrate 0.7485 CYP450 2D6 substrate Non-substrate 0.8558 CYP450 3A4 substrate Substrate 0.7356 CYP450 1A2 substrate Inhibitor 0.8341 CYP450 2C9 inhibitor Non-inhibitor 0.5206 CYP450 2D6 inhibitor Non-inhibitor 0.8462 CYP450 2C19 inhibitor Inhibitor 0.6555 CYP450 3A4 inhibitor Non-inhibitor 0.5194 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7292 Ames test Non AMES toxic 0.7848 Carcinogenicity Non-carcinogens 0.7554 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.3701 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9974 hERG inhibition (predictor II) Non-inhibitor 0.8359
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 177.937442 predictedDarkChem Lite v0.1.0 [M-H]- 161.21156 predictedDeepCCS 1.0 (2019) [M+H]+ 178.545642 predictedDarkChem Lite v0.1.0 [M+H]+ 163.56956 predictedDeepCCS 1.0 (2019) [M+Na]+ 178.598342 predictedDarkChem Lite v0.1.0 [M+Na]+ 169.67747 predictedDeepCCS 1.0 (2019)
Targets
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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
- Substrate
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Hedrich WD, Hassan HE, Wang H: Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425. doi: 10.1016/j.apsb.2016.07.016. Epub 2016 Aug 9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C18
- Uniprot ID
- P33260
- Uniprot Name
- Cytochrome P450 2C18
- Molecular Weight
- 55710.075 Da
References
- Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A: Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs. Biol Pharm Bull. 2005 Sep;28(9):1711-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A: Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs. Biol Pharm Bull. 2005 Sep;28(9):1711-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A: Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs. Biol Pharm Bull. 2005 Sep;28(9):1711-6. [Article]
Drug created at July 31, 2007 13:10 / Updated at May 14, 2021 01:05