clomethiazole 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
602 533-45-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • chlormethiazole
  • clomethiazole
  • chlorethiazol
  • chlorethiazole
  • chlormethiazol
  • clomethiazolum
  • distraneurin
  • emineurina
  • chlormethiazole hydrochloride
  • chlormethiazole HCl
  • clomethiazole edisilate
A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.
  • Molecular weight: 161.65
  • Formula: C6H8ClNS
  • CLOGP: 1.98
  • LIPINSKI: 0
  • HAC: 1
  • HDO: 0
  • TPSA: 12.89
  • ALOGS: -2.38
  • ROTB: 2

Drug dosage:

DoseUnitRoute
1.50 g O
1.50 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 10 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.05 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 33.94 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 25 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 6.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 33 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.36 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 4.50 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.952 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.373 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 82.985 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 71.285 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 68.130 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 45.810 % High 1
herg hERG pIC50 3.965 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 8.954 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 38.459 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 47.580 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,MAPK7,PDK1,PDK2,PDK4,PRKDC,TEK 16
kinase-selectivity-class GRK2 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.302 High 1
mh-clint Mouse hepatocyte intrinsic clearance 121.619 High 1
mppb Mouse plasma protein binding (% unbound) 67.980 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.094 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 64.590 % High 1
rh-clint Rat hepatocyte intrinsic clearance 25.235 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 95.670 % High 1
rppb Rat plasma protein binding (% unbound) 56.190 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 46.881 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1981 YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Vascular encephalopathy 135.73 61.90 20 968 750 90626709
Subileus 117.26 61.90 22 966 3622 90623837
Gastrointestinal sounds abnormal 100.27 61.90 20 968 4523 90622936
Abdominal tenderness 85.94 61.90 20 968 9304 90618155
Faecaloma 78.55 61.90 19 969 10412 90617047
Ileus 74.55 61.90 20 968 16526 90610933
Dementia 67.31 61.90 20 968 23841 90603618
Bladder disorder 62.88 61.90 16 972 10756 90616703

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug withdrawal convulsions 63.93 44.35 12 678 1326 42619319

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Vascular encephalopathy 127.15 43.46 20 1703 804 110586772
Subileus 96.84 43.46 22 1701 6415 110581161
Gastrointestinal sounds abnormal 87.46 43.46 20 1703 5998 110581578
Drug interaction 75.24 43.46 62 1661 500121 110087455
Abdominal tenderness 73.01 43.46 20 1703 12437 110575139
Depressed level of consciousness 65.97 43.46 33 1690 112245 110475331
Faecaloma 65.02 43.46 19 1704 14889 110572687
Dementia 58.38 43.46 21 1702 31652 110555924
Drug withdrawal convulsions 57.09 43.46 12 1711 2437 110585139
Bladder disorder 56.63 43.46 16 1707 11121 110576455
Ileus 55.24 43.46 20 1703 30709 110556867
Neuroleptic malignant syndrome 53.23 43.46 20 1703 34039 110553537

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05CM02 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Other hypnotics and sedatives
ATC N05CX04 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Hypnotics and sedatives in combination, excl. barbiturates
MeSH PA D000927 Anticonvulsants
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D006993 Hypnotics and Sedatives
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018682 GABA Agents
MeSH PA D018696 Neuroprotective Agents
MeSH PA D018757 GABA Modulators
MeSH PA D020011 Protective Agents

Related Drugs by ATC class:

N05CM Other hypnotics and sedatives 13 drugs
apronalbromisovalcarbromaldexmedetomidineethchlorvynolhexapropymatemethaqualonemethylpentynolniaprazinepropiomazinescopolaminetriclofos show all 13 →
N05CX Hypnotics and sedatives in combination, excl. barbiturates 5 drugs
dipiperonylaminoethanolemeproniummeprobamatemethaqualonemethylpentynol

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Alcohol withdrawal syndrome indication 191480000
Insomnia indication 193462001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.16 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
GABA-A receptor alpha-1/beta-3/gamma-2 Ion channel WOMBAT-PK

External reference:

IDSource
N0000167093 NUI
D07330 KEGG_DRUG
20802 RXNORM
C0008221 UMLSCUI
CHEBI:92875 CHEBI
CHEMBL315795 ChEMBL_ID
DB06470 DRUGBANK_ID
10783 PUBCHEM_CID
1717 INN_ID
0C5DBZ19HV UNII
003691 NDDF
003692 NDDF
354039005 SNOMEDCT_US
395978007 SNOMEDCT_US
395988008 SNOMEDCT_US
D002719 MESH_DESCRIPTOR_UI

Pharmaceutical products:

None