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Identification
NameClotiazepam
Accession NumberDB01559
Typesmall molecule
Groupsapproved, illicit
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.

Structure
Thumb
Synonyms
SynonymLanguageCode
ClotiazepamumLatinINN
SaltsNot Available
Brand names
NameCompany
ClozanPfizer
DistensanEsteve
RizeDae Woong
RizenFormenti
TienorFarmaka
Brand mixturesNot Available
Categories
CAS number33671-46-4
WeightAverage: 318.821
Monoisotopic: 318.059361509
Chemical FormulaC16H15ClN2OS
InChI KeyCHBRHODLKOZEPZ-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassThienodiazepines
SubclassNot Available
Direct parentThienodiazepines
Alternative parents1,4-Diazepines; Chlorobenzenes; Aryl Chlorides; Thiophenes; Tertiary Carboxylic Acid Amides; Tertiary Amines; Polyamines; Carboxylic Acids; Organochlorides
Substituentspara-diazepine; chlorobenzene; aryl chloride; benzene; aryl halide; thiophene; tertiary carboxylic acid amide; tertiary amine; carboxamide group; polyamine; carboxylic acid derivative; carboxylic acid; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the thienodiazepines. These are heteropolycyclic containing a thiophene ring fused to a diazepine ring.
Pharmacology
IndicationFor the treatment of anxiety disorders.
PharmacodynamicsClotiazepam is a benzodiazepine derivative possessing anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Stage 2 NREM sleep is significantly increased by clotiazepam.
Mechanism of actionClotiazepam 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding99% bound to plasma proteins.
Metabolism

Hepatic.

Route of eliminationNot Available
Half life4 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.5206
CYP450 2D6 substrate Non-inhibitor 0.8462
CYP450 2C19 substrate Inhibitor 0.6555
CYP450 3A4 substrate 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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point105-106Nakanishi, 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 solubility5.37e-03 g/lALOGPS
logP3.58ALOGPS
logP4.11ChemAxon
logS-4.8ALOGPS
pKa (strongest basic)2.39ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area32.67ChemAxon
rotatable bond count2ChemAxon
refractivity85.66ChemAxon
polarizability33.01ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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 Reference
  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
External Links
ResourceLink
PubChem Compound2811
PubChem Substance46508776
ChemSpider2709
Therapeutic Targets DatabaseDAP000932
PharmGKBPA164752437
WikipediaClotiazepam
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

References:

  1. Baburin I, Khom S, Timin E, Hohaus A, Sieghart W, Hering S: Estimating the efficiency of benzodiazepines on GABA receptors comprising gamma1 or gamma2 subunits. Br J Pharmacol. 2008 Oct;155(3):424-33. Epub 2008 Jul 7. Pubmed
  2. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

2. Gamma-aminobutyric acid receptor subunit alpha-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

3. Gamma-aminobutyric acid receptor subunit alpha-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

4. Gamma-aminobutyric acid receptor subunit alpha-5

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

5. Gamma-aminobutyric acid receptor subunit gamma-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details

References:

  1. Baburin I, Khom S, Timin E, Hohaus A, Sieghart W, Hering S: Estimating the efficiency of benzodiazepines on GABA receptors comprising gamma1 or gamma2 subunits. Br J Pharmacol. 2008 Oct;155(3):424-33. Epub 2008 Jul 7. Pubmed
  2. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

6. Gamma-aminobutyric acid receptor subunit gamma-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details

References:

  1. Baburin I, Khom S, Timin E, Hohaus A, Sieghart W, Hering S: Estimating the efficiency of benzodiazepines on GABA receptors comprising gamma1 or gamma2 subunits. Br J Pharmacol. 2008 Oct;155(3):424-33. Epub 2008 Jul 7. Pubmed
  2. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

7. Gamma-aminobutyric acid receptor subunit gamma-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

8. Gamma-aminobutyric acid receptor subunit beta-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

9. Gamma-aminobutyric acid receptor subunit beta-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details

References:

  1. Baburin I, Khom S, Timin E, Hohaus A, Sieghart W, Hering S: Estimating the efficiency of benzodiazepines on GABA receptors comprising gamma1 or gamma2 subunits. Br J Pharmacol. 2008 Oct;155(3):424-33. Epub 2008 Jul 7. Pubmed

10. Gamma-aminobutyric acid receptor subunit beta-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

11. Gamma-aminobutyric acid receptor subunit delta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

12. Gamma-aminobutyric acid receptor subunit epsilon

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

13. Gamma-aminobutyric acid receptor subunit pi

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

14. Gamma-aminobutyric acid receptor subunit rho-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit rho-1 P24046 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

15. Gamma-aminobutyric acid receptor subunit rho-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit rho-2 P28476 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

16. Gamma-aminobutyric acid receptor subunit rho-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit rho-3 A8MPY1 Details

References:

  1. Mandrioli R, Mercolini L, Raggi MA: Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. Pubmed

Enzymes

1. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. 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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C18

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C18 P33260 Details

References:

  1. 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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. 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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. 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. Epub 2009 Nov 24. Pubmed

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Drug created on July 31, 2007 07:10 / Updated on April 09, 2014 12:17