This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Clomethiazole
Accession Number
DB06470
Type
Small Molecule
Groups
Investigational
Description

Clomethiazole is a well-established γ-aminobutyric acid (GABAA)-mimetic drug. It is a sedative and hypnotic that is widely used in treating and preventing symptoms of acute alcohol withdrawal. It is a drug which is structurally related to thiamine (vitamin B1) but acts like a sedative, hypnotic, muscle relaxant and anticonvulsant. It is also used for the management of agitation, restlessness, short-term insomnia and Parkinson's disease in the elderly.

Structure
Thumb
Synonyms
  • Clometiazol
Product Ingredients
IngredientUNIICASInChI Key
Clomethiazole hydrochloride85223EMG446001-74-7OFXYKSLKNMTBHK-UHFFFAOYSA-N
International/Other Brands
Zendra
Categories
UNII
0C5DBZ19HV
CAS number
Not Available
Weight
Average: 161.65
Monoisotopic: 161.0065981
Chemical Formula
C6H8ClNS
InChI Key
PCLITLDOTJTVDJ-UHFFFAOYSA-N
InChI
InChI=1S/C6H8ClNS/c1-5-6(2-3-7)9-4-8-5/h4H,2-3H2,1H3
IUPAC Name
5-(2-chloroethyl)-4-methyl-1,3-thiazole
SMILES
CC1=C(CCCl)SC=N1

Pharmacology

Indication

Investigated for use/treatment in strokes.

Pharmacodynamics
Not Available
Mechanism of action

clomethiazole interacts with the GABAA receptor complex. It inhibits the binding of [35S]butyl-bicyclophosphorothionate (TBPS), an effect indicative of GABAA receptor-channel activation, by increasing the rate of [35S]TBPS dissociation and decreasing the binding affinity. Gamma-aminobutyric acid (GABA), acting at GABAA receptors, is the main fast inhibitory neurotransmitter in mammalian central nervous system

TargetActionsOrganism
UGamma-aminobutyric acid receptor subunit alpha-1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with clomethiazole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with clomethiazole.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Clomethiazole is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineClomethiazole may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Clomethiazole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with clomethiazole.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Clomethiazole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with clomethiazole.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Clomethiazole.
5-androstenedioneThe metabolism of clomethiazole can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

General References
  1. Lyden PD, Ashwood T, Claesson L, Odergren T, Friday GH, Martin-Munley S: The clomethiazole acute stroke study in ischemic, hemorrhagic, and t-PA treated stroke: Design of a phase III trial in the united states and canada. J Stroke Cerebrovasc Dis. 1998 Nov-Dec;7(6):435-41. [PubMed:17895123]
  2. Millis SR, Straube D, Iramaneerat C, Smith EV Jr, Lyden P: Measurement properties of the National Institutes of Health Stroke Scale for people with right- and left-hemisphere lesions: further analysis of the clomethiazole for acute stroke study-ischemic (class-I) trial. Arch Phys Med Rehabil. 2007 Mar;88(3):302-8. [PubMed:17321821]
External Links
PubChem Compound
10783
PubChem Substance
347827773
ChemSpider
10327
BindingDB
234400
ChEBI
92875
ChEMBL
CHEMBL315795
Wikipedia
Chlormethiazole
ATC Codes
N05CX04 — Clomethiazole, combinationsN05CM02 — Clomethiazole

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.674 mg/mLALOGPS
logP2.47ALOGPS
logP1.77ChemAxon
logS-2.4ALOGPS
pKa (Strongest Basic)3.18ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.89 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity40.37 m3·mol-1ChemAxon
Polarizability16.14 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4,5-disubstituted thiazoles. These are compounds containing a thiazole ring substituted at positions 4 and 5 only.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Thiazoles
Direct Parent
4,5-disubstituted thiazoles
Alternative Parents
Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
Substituents
4,5-disubstituted 1,3-thiazole / Heteroaromatic compound / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Organochloride / Organohalogen compound / Alkyl halide
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
a thiazole (CPD-10432)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
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. 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]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
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. 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]
Kind
Protein
Organism
Human
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. 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]

Drug created on March 19, 2008 10:34 / Updated on November 03, 2018 15:41