Clobazam (CHEM003524)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (18)XML
Record Information
Version1.0
Creation Date2014-08-30 21:05:04 UTC
Update Date2026-03-31 19:07:26 UTC
Accession NumberCHEM003524
Identification
Common NameClobazam
ClassSmall Molecule
DescriptionClobazam belongs to the 1,5-benzodiazepine class of drugs and is expected to have a better side-effect profile compared to older 1,4-benzodiazepines. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. The oral preparation was FDA approved on October 21, 2011. An oral suspension is expected to be available in 2013.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • Suspected Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Anticonvulsant
  • Benzodiazepine
  • Drug
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
1-Phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepineChEBI
7-Chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dioneChEBI
ClobazamumChEBI
MystanKegg
OnfiKegg
UrbanylHMDB
FrisiumHMDB
1-Phenyl-5-methyl-8-chloro-1,2,4,5- tetrahydro-2,4-diketo-3H-1,5-benzodiazepineHMDB
Chemical FormulaC16H13ClN2O2
Average Molecular Mass300.740 g/mol
Monoisotopic Mass300.067 g/mol
CAS Registry Number22316-47-8
IUPAC Name7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione
Traditional Nameclobazam
SMILESCN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O
InChI IdentifierInChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3
InChI KeyCXOXHMZGEKVPMT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub ClassNot Available
Direct ParentBenzodiazepines
Alternative Parents
Substituents
  • Benzodiazepine
  • Para-diazepine
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • 1,3-dicarbonyl compound
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Lactam
  • Carboxamide group
  • Carboxylic acid derivative
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point180-182°C
Boiling PointNot Available
Solubility188 mg/L
Predicted Properties
PropertyValueSource
Water Solubility0.16 g/LALOGPS
logP2.14ALOGPS
logP2.55ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)4.07ChemAxon
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area40.62 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity80.3 m³·mol⁻¹ChemAxon
Polarizability30.07 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-053r-0290000000-85c722aae16a6c4f1e1aSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0090000000-3b46d60abcc8dfacf4d8Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0019000000-71512d7a18cf60430dd9Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-0092000000-e687a1e3760fb870dbc9Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-0090000000-d450ded1f22039f00b63Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0ab9-0190000000-e4211cbc2957a587e3d3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05fr-0590000000-51f4fa0445c2d047ef6bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0g4j-1960000000-a89e1c91bfa7b974be48Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014j-4920000000-93c0877b3acf519d2b98Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-016u-7900000000-bc29714be08b6ae4120bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0hi6-9600000000-7c6a3974d95a0015757eSpectrum
LC-MS/MSLC-MS/MS Spectrum - -1V, Positivesplash10-0a4i-0090000000-f8bfd7fb18f6c2191b61Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-0udi-0019000000-71512d7a18cf60430dd9Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-05fr-0590000000-d54a49898cc15a62a5e6Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0ab9-0190000000-55d5faa9832676ff3cbeSpectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0a4i-0092000000-ea34c0db78be09efb678Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0a4i-0090000000-35ff57d7b80e2c98ae57Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-0g4j-1960000000-cf4e19e49420cb7d7a8fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-c177e3ba787d31e6efa9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-1019000000-ecf7835c598275ee85fbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0f6x-9560000000-ac11ec0388fbae849904Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-5aff96d7f16fb8885018Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-38aef9b903ce595b395dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f9f-4490000000-02ff5e375a7cffbef887Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-d5f71cf6ca39e39e4e90Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0069000000-00f02d6bca08146095d7Spectrum
MSMass Spectrum (Electron Ionization)splash10-0pb9-6392000000-a76f30f353b3407df0c6Spectrum
Toxicity Profile
Route of ExposureAfter oral administration of clobazam, it is almost completely absorbed (87% of dose). Bioavailability relative to solution was almost at 100%. Food does not affect absorption. Tmax = 1-3 hours.
Mechanism of ToxicityClobazam binds at distinct binding sites associated with the chloride ionopore at the post-synaptic GABA receptor. These GABA receptors are in various locations in the CNS (limbic, reticular formation) and clobazam increases the duration of time for which the chloride ionopore is open. As a result, hyper polarization and stabilization of the membrane occur as the post-synaptic inhibitory effect of GABA is enhanced.
MetabolismClobazam is extensively metabolized in the liver via N-demethylation and hydroxylation. Clobazam has two major metabolites: N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, the former of which is active. Norclobazam is one-fourth the potency of clobazam. The main enzyme that facilitates the process of N-demethylation is CYP3A4, and to a lesser extent by CYP2C19 and CYP2B6. Norclobazam itself is also metabolized via hydroxylation, primarily by CYP2C19. The formation of 4'-hydroxyclobazam is facilitated by CYP2C18 and CYP2C19. A factor in determining extent of metabolism is the genetic profile of the individual patient as CYP2C19 is a polymorphic enzyme. Route of Elimination: Clobazam is eliminated via the urine (~94%) as metabolites. Half Life: The mean elimination half life of an oral dose of clobazam 40 mg is 32 hours. It's main metabolite, norclobazam, as a half life of 57 hours. The half life in adult patients with epilepsy are higher than those that are healthy.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor treatment and management of epilepsy and seizures associated with Lennox-Gastaut syndrome, a difficult-to-treat form of childhood epilepsy.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsThe most common adverse effects include somnolence, pyrexia, upper respiratory tract infection, and lethargy.
TreatmentGeneral supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.
Concentrations
Not Available
DrugBank IDDB00349
HMDB IDHMDB0014493
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkClobazam
Chemspider ID2687
ChEBI ID31413
PubChem Compound ID2789
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Hauptmann, K.H., Weber, K.-H., Zeile, K., Danneberg, P. and Giesemann, R.; South African
Patent 68/0803; February 7,1968; assigned to Boehringer lngelheim GmbH, Germany.

MSDSNot Available
General References
1. Freche C: [Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]. Sem Hop Ther. 1975 Apr;51(4):261-3.
2. Authors unspecified: Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group. Epilepsia. 1991 May-Jun;32(3):407-16.
3. Wildin JD, Pleuvry BJ, Mawer GE, Onon T, Millington L: Respiratory and sedative effects of clobazam and clonazepam in volunteers. Br J Clin Pharmacol. 1990 Feb;29(2):169-77.
4. Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44.
5. Giarratano M, Standley K, Benbadis SR: Clobazam for treatment of epilepsy. Expert Opin Pharmacother. 2012 Feb;13(2):227-33. doi: 10.1517/14656566.2012.647686. Epub 2012 Jan 13.
6. Walzer M, Bekersky I, Blum RA, Tolbert D: Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012 Apr;32(4):340-53. doi: 10.1002/j.1875-9114.2012.01028.x. Epub 2012 Mar 15.
7. Yang LP, Scott LJ: Clobazam : in patients with Lennox-Gastaut syndrome. CNS Drugs. 2012 Nov;26(11):983-91. doi: 10.1007/s40263-012-0007-0.
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