U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C16H13ClN2O2
Molecular Weight 300.74
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLOBAZAM

SMILES

CN1C2=CC=C(Cl)C=C2N(C3=CC=CC=C3)C(=O)CC1=O

InChI

InChIKey=CXOXHMZGEKVPMT-UHFFFAOYSA-N
InChI=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

HIDE SMILES / InChI

Molecular Formula C16H13ClN2O2
Molecular Weight 300.74
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Clobazam belongs to the 1,5-benzodiazepine class of drugs with antiepileptic properties. It has been used to treat anxiety and epilepsy since 1970s. In the US clobazam was approved for marketing in October of 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. It is also approved for adjunctive therapy for epilepsy in patients who have not responded to first-line drugs and in children who are refractory to first-line drugs. The mechanism of action for clobazam is not fully understood but is thought to involve what is known as potentiation of GABAergic neurotransmission resulting from binding at a benzodiazepine site at the GABA(A) receptor. Possible side effects: constipation, fever, drowsiness, sedation, ataxia, aggressive behavior, lethargy, drooling, and irritability. Other side effects include: urinary tract infection, pneumonia, cough, dysphagia, dysarthria, bronchitis, insomnia, fatigue, decreased appetite, and increased appetite.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
Therapeutic drug monitoring of old and newer anti-epileptic drugs.
2004
Hypersensitivity to topiramate sprinkle capsules does not preclude the use of topiramate tablets.
2004
Development of a whole body physiologically based model to characterise the pharmacokinetics of benzodiazepines. 1: Estimation of rat tissue-plasma partition ratios.
2004 Aug
Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.
2004 Aug
A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam.
2004 Dec
[Idiopathic epilepsies: some therapeutic aspects].
2004 Jan 16-31
Sporadic major hyperekplexia in neonates and infants: clinical manifestations and outcome.
2004 Jul
Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models.
2004 Jul
Forensic intoxication with clobazam: HPLC/DAD/MSD analysis.
2004 Jul 16
In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19.
2004 Nov
Affinity of various benzodiazepine site ligands in mice with a point mutation in the GABA(A) receptor gamma2 subunit.
2004 Oct 15
Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations.
2004 Sep
The difficulty in diagnosing non-convulsive status epilepticus during routine medical practice.
2004 Sep
Management of Landau-Kleffner syndrome.
2005
Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies.
2005
Photosensitivity in idiopathic generalized epilepsies.
2005
Levetiracetam in the treatment of infantile spasms.
2005
[Subacute encephalitis with anti-glutamate receptor antibodies presented with epilepsia partialis continua].
2005 Aug
Molecular regulation of glutamate and GABA transporter proteins by clobazam during epileptogenesis in Fe(+++)-induced epileptic rats.
2005 Dec 14
Treatment of electrical status epilepticus during slow-wave sleep with high-dose corticosteroid.
2005 Jan
[Antiepileptic drugs in the treatment of autistic regression syndromes].
2005 Jan 15
Stiripentol.
2005 Jul
Neuroembryopathic effect of clobazam in rat: a histological study.
2005 Jun
A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the Lennox-Gastaut syndrome.
2005 Jun
Motor impairment on awakening in a patient with an EEG pattern of "unilateral, continuous spikes and waves during slow sleep".
2005 Jun
Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid by LC-MS/MS.
2005 Jun 10
Evaluation of health status in epilepsy using the EQ-5D questionnaire: a prospective, observational, 6-month study of adjunctive therapy with anti-epileptic drugs.
2005 May
Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry.
2005 Oct 15
Simultaneous determination of clobazam and its major metabolite in human plasma by a rapid HPLC method.
2005 Sep 5
Levetiracetam in idiopathic generalised epilepsy and porphyria cutanea tarda.
2006
[Epilepsy with electrical status epilepticus during slow sleep: diagnostic criteria and approaches to therapy].
2006
Stiripentol, a putative antiepileptic drug, enhances the duration of opening of GABA-A receptor channels.
2006 Apr
In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism.
2006 Apr
Landau-Kleffner syndrome is not an eponymic badge of ignorance.
2006 Aug
Effects of some antiepileptics on septal-kindled seizures in rats.
2006 Dec
[Epilepsy: which therapy in acute care?].
2006 Dec 8
Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro.
2006 Feb
Pharmacological properties of GABAA receptors containing gamma1 subunits.
2006 Feb
Eye rolling as a manifestation of clobazam toxicity in a child with epilepsy.
2006 Jul
Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas.
2006 Jun
Benign angiopathy of the central nervous system associated with phenytoin intoxication.
2006 Jun
Abusive prescription of psychostimulants: a study of two cases.
2006 Mar
Clobazam as add-on therapy in children with epileptic encephalopathy.
2006 May
Oxidative stress in children receiving valproic acid.
2006 Nov
Quantification of benzodiazepines in whole blood and serum.
2006 Nov
Treatment in the pediatric emergency department is evidence based: a retrospective analysis.
2006 Oct 6
Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy.
2006 Sep
The detection of sedatives in hair and nail samples using tandem LC-MS-MS.
2007 Feb 14
Clobazam.
2007 Jan
Stiripentol.
2007 Jan
Patents

Sample Use Guides

In Vivo Use Guide
Patients ≤30 kg body weight: Initiate at 5 mg daily and titrate as tolerated up to 20 mg daily. Patients > 30 kg body weight: Initiate at 10 mg daily and titrate as tolerated up to 40 mg daily. For doses above 5 mg/day administer in two divided doses. Dosage adjustment needed in following groups: Geriatric patients. Known CYP2C19 poor metabolizers. Mild or moderate hepatic impairment; no information for severe hepatic impairment.
Route of Administration: Oral
In Vitro Use Guide
Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact corticohippocampal formations (CHFs) of P7-8 rats, and extracellular recordings were performed in the hippocampus and neocortex. Clobazam was applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Clobazam prevented the occurrence of seizures in recurrent ictal-like seizures.
Substance Class Chemical
Created
by admin
on Tue Oct 22 00:30:04 UTC 2019
Edited
by admin
on Tue Oct 22 00:30:04 UTC 2019
Record UNII
2MRO291B4U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLOBAZAM
DASH   EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
CLOBAZAM [MI]
Common Name English
CLOBAZAM [JAN]
Common Name English
URBADAN
Brand Name English
1H-1,5-BENZODIAZEPINE-2,4(3H,5H)-DIONE, 7-CHLORO-1-METHYL-5-PHENYL-
Systematic Name English
CLOBAZAM [ORANGE BOOK]
Common Name English
CLOBAZAM [VANDF]
Common Name English
FRISIUM
Brand Name English
URBANYL
Brand Name English
ONFI
Brand Name English
LM 2717
Code English
LM-2717
Code English
CLOBAZAM [EP]
Common Name English
COLBAZAM [VANDF]
Common Name English
NSC-336279
Code English
HR-376
Code English
MYSTAN
Brand Name English
H 4723
Code English
HR 376
Code English
CLOBAZAM [MART.]
Common Name English
7-CHLORO-1-METHYL-5-PHENYL-1H-1,5-BENZODIAZEPINE-2,4-(3H,5H)-DIONE
Common Name English
SYMPAZAN
Brand Name English
H-4723
Code English
CLOBAZAM [INN]
Common Name English
CLOBAZAM [USAN]
Common Name English
CLOBAZAM [WHO-DD]
Common Name English
Classification Tree Code System Code
DEA NO. 2751
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
FDA ORPHAN DRUG 248307
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
LIVERTOX 218
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
WHO-ATC N05BA09
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
NCI_THESAURUS C28197
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
WHO-VATC QN05BA09
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
NDF-RT N0000175694
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
Code System Code Type Description
CAS
22316-47-8
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
WIKIPEDIA
CLOBAZAM
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
LactMed
22316-47-8
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
MESH
C012255
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
EPA CompTox
22316-47-8
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
PUBCHEM
2789
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
INN
3055
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
DRUG BANK
DB00349
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
EVMPD
SUB06673MIG
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
ChEMBL
CHEMBL70418
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
HSDB
22316-47-8
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
NCI_THESAURUS
C81615
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
ECHA (EC/EINECS)
244-908-7
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
RXCUI
21241
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY RxNorm
MERCK INDEX
M3626
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY Merck Index
NDF-RT
N0000182137
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
IUPHAR
7149
Created by admin on Tue Oct 22 00:30:04 UTC 2019 , Edited by admin on Tue Oct 22 00:30:04 UTC 2019
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INDUCER
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
Clobazam is cleared mainly by metabolism with subsequent renal elimination of metabolites. In a mass balance study, 82% of the dose administered was recovered in the urine and 11% in the feces. Clobazam represents ~2 % of the dose recovered in urine.
URINE
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
METABOLITE ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC SINGLE- OR MULTIPLE-DOSE ADMINISTRATIONS