Identification

Name
Clotiazepam
Accession Number
DB01559
Description

Clotiazepam is a benzodiazepine derivative, 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
Thumb
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.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Clotiazepam is a benzodiazepine derivative 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.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
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
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbametapirThe serum concentration of Clotiazepam can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Clotiazepam can be increased when combined with Abatacept.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Clotiazepam.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Clotiazepam.
AclidiniumClotiazepam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AdalimumabThe metabolism of Clotiazepam can be increased when combined with Adalimumab.
AgomelatineThe risk or severity of adverse effects can be increased when Clotiazepam is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Clotiazepam.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Clotiazepam.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Clotiazepam.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

International/Other Brands
Clozan (Pfizer) / Distensan (Esteve) / Rize (Dae Woong) / Rizen (Formenti) / Tienor (Farmaka)

Categories

ATC Codes
N05BA21 — Clotiazepam
Drug Categories
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

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
  1. 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. [PubMed:709]
Human Metabolome Database
HMDB0015512
KEGG Drug
D01328
PubChem Compound
2811
PubChem Substance
46508776
ChemSpider
2709
RxNav
2622
ChEBI
31425
ChEMBL
CHEMBL1697737
ZINC
ZINC000000001207
Therapeutic Targets Database
DAP000932
PharmGKB
PA164752437
Wikipedia
Clotiazepam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherBioequivalence1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Solution / dropsOral10 MG/ML
Tablet10 MG
Tablet5 MG
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)105-106Nakanishi, M., Araki, K.,Tahara, T. and Shiroki, M.; US. Patent 3,849,405; November 19, 1974; assigned to Yoshitomi Pharmaceutical Industries, Ltd.
logP3.18MARUYAMA,T ET AL. (1992)
Predicted Properties
PropertyValueSource
Water Solubility0.00537 mg/mLALOGPS
logP3.58ALOGPS
logP4.11ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.67 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity85.66 m3·mol-1ChemAxon
Polarizability33.01 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9849
Blood Brain Barrier+0.97
Caco-2 permeable+0.662
P-glycoprotein substrateSubstrate0.6147
P-glycoprotein inhibitor INon-inhibitor0.7404
P-glycoprotein inhibitor IINon-inhibitor0.7762
Renal organic cation transporterNon-inhibitor0.5527
CYP450 2C9 substrateNon-substrate0.7485
CYP450 2D6 substrateNon-substrate0.8558
CYP450 3A4 substrateSubstrate0.7356
CYP450 1A2 substrateInhibitor0.8341
CYP450 2C9 inhibitorNon-inhibitor0.5206
CYP450 2D6 inhibitorNon-inhibitor0.8462
CYP450 2C19 inhibitorInhibitor0.6555
CYP450 3A4 inhibitorNon-inhibitor0.5194
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7292
Ames testNon AMES toxic0.7848
CarcinogenicityNon-carcinogens0.7554
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3701 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9974
hERG inhibition (predictor II)Non-inhibitor0.8359
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-014u-3494000000-432038f1e527960b02fc
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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
  1. 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. [PubMed:23038269]
  2. 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. [PubMed:29950725]
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
  1. 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. [PubMed:23038269]
  2. 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. [PubMed:29950725]

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
  1. 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. [PubMed:27709010]
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
  1. 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. [PubMed:16141545]
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
  1. 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. [PubMed:16141545]
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
  1. 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. [PubMed:16141545]

Drug created on July 31, 2007 07:10 / Updated on June 12, 2020 10:51

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