CLOBAZAM

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 Search

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 186	Activator 1315	Lennox Gastaut Syndrome

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lennox Gastaut Syndrome 7	Secondary	GABA-A receptor; anion channel	Approved 7883	ONFI
[Alcohol withdrawal syndrome, Anxiety] 1			Approved (off-label) 8

PubMed

Title	Date	PubMed
Therapeutic drug monitoring of old and newer anti-epileptic drugs.	2004	15576287
Hypersensitivity to topiramate sprinkle capsules does not preclude the use of topiramate tablets.	2004	15035654
Development of a whole body physiologically based model to characterise the pharmacokinetics of benzodiazepines. 1: Estimation of rat tissue-plasma partition ratios.	2004 Aug	15563004
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	15329838
A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam.	2004 Dec	15533655
[Idiopathic epilepsies: some therapeutic aspects].	2004 Jan 16-31	14752722
Sporadic major hyperekplexia in neonates and infants: clinical manifestations and outcome.	2004 Jul	15246489
Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models.	2004 Jul	15158698
Forensic intoxication with clobazam: HPLC/DAD/MSD analysis.	2004 Jul 16	15240045
In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19.	2004 Nov	15483195
Affinity of various benzodiazepine site ligands in mice with a point mutation in the GABA(A) receptor gamma2 subunit.	2004 Oct 15	15451405
Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations.	2004 Sep	15319339
The difficulty in diagnosing non-convulsive status epilepticus during routine medical practice.	2004 Sep	15315926
Management of Landau-Kleffner syndrome.	2005	16356025
Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies.	2005	16302888
Photosensitivity in idiopathic generalized epilepsies.	2005	16302877
Levetiracetam in the treatment of infantile spasms.	2005	15701562
[Subacute encephalitis with anti-glutamate receptor antibodies presented with epilepsia partialis continua].	2005 Aug	16180713
Molecular regulation of glutamate and GABA transporter proteins by clobazam during epileptogenesis in Fe(+++)-induced epileptic rats.	2005 Dec 14	16274841
Treatment of electrical status epilepticus during slow-wave sleep with high-dose corticosteroid.	2005 Jan	15607609
[Antiepileptic drugs in the treatment of autistic regression syndromes].	2005 Jan 15	15736083
Stiripentol.	2005 Jul	16022579
Neuroembryopathic effect of clobazam in rat: a histological study.	2005 Jun	16295712
A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the Lennox-Gastaut syndrome.	2005 Jun	15943601
Motor impairment on awakening in a patient with an EEG pattern of "unilateral, continuous spikes and waves during slow sleep".	2005 Jun	15929915
Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid by LC-MS/MS.	2005 Jun 10	15944062
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	15969872
Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry.	2005 Oct 15	16154525
Simultaneous determination of clobazam and its major metabolite in human plasma by a rapid HPLC method.	2005 Sep 5	16005690
Levetiracetam in idiopathic generalised epilepsy and porphyria cutanea tarda.	2006	17163270
[Epilepsy with electrical status epilepticus during slow sleep: diagnostic criteria and approaches to therapy].	2006	16737153
Stiripentol, a putative antiepileptic drug, enhances the duration of opening of GABA-A receptor channels.	2006 Apr	16650136
In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism.	2006 Apr	16415114
Landau-Kleffner syndrome is not an eponymic badge of ignorance.	2006 Aug	16806832
Effects of some antiepileptics on septal-kindled seizures in rats.	2006 Dec	16938433
[Epilepsy: which therapy in acute care?].	2006 Dec 8	17136662
Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro.	2006 Feb	16505575
Pharmacological properties of GABAA receptors containing gamma1 subunits.	2006 Feb	16272224
Eye rolling as a manifestation of clobazam toxicity in a child with epilepsy.	2006 Jul	16780634
Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas.	2006 Jun	16804259
Benign angiopathy of the central nervous system associated with phenytoin intoxication.	2006 Jun	16376047
Abusive prescription of psychostimulants: a study of two cases.	2006 Mar	16566781
Clobazam as add-on therapy in children with epileptic encephalopathy.	2006 May	16736732
Oxidative stress in children receiving valproic acid.	2006 Nov	17095346
Quantification of benzodiazepines in whole blood and serum.	2006 Nov	16220317
Treatment in the pediatric emergency department is evidence based: a retrospective analysis.	2006 Oct 6	17022829
Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy.	2006 Sep	17057871
The detection of sedatives in hair and nail samples using tandem LC-MS-MS.	2007 Feb 14	16707239
Clobazam.	2007 Jan	17199029
Stiripentol.	2007 Jan	17199026

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

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Name

Type

Language

CLOBAZAM

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