CLOBAZAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H13ClN2O2
Molecular Weight	300.7402
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1c2ccc(cc2N(c3ccccc3)C(=O)CC1=O)Cl

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	300.7402
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202067s003,203993s003lbl.pdf
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/cdi/clobazam.html; http://www.epilepsy.com/medications/clobazam https://www.ncbi.nlm.nih.gov/pubmed/?term=23318278

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 189 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22145708	Activator 1337

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lennox-Gastaut syndrome 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202067s002,203993s002lbl.pdf	Secondary		Approved 8003	ONFI Approved Use Indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older. Launch Date 1.31915514E12

C_max

Value	Dose	Co-administered	Analyte	Population
641 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6529527/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOBAZAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
13741 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6529527/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOBAZAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
36 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202067s005,203993s007lbl.pdf	30 mg 1 times / day unknown, oral dose: 30 mg route of administration: Oral experiment type: UNKNOWN co-administered:		CLOBAZAM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202067s005,203993s007lbl.pdf	30 mg 1 times / day unknown, oral dose: 30 mg route of administration: Oral experiment type: UNKNOWN co-administered:		CLOBAZAM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 mg 2 times / day steady, oral Highest studied dose Dose: 80 mg, 2 times / day Route: oral Route: steady Dose: 80 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69-70	healthy n = 70 Health Status: healthy Population Size: 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69-70	Disc. AE: Somnolence, Depressed mood... Other AEs: Delirium... AEs leading to discontinuation/dose reduction: Somnolence (1 patient) Depressed mood (1 patient) Libido decreased (1 patient) Erectile dysfunction (1 patient) Insomnia (1 patient) Dysarthria (1 patient) Unsteady gait (1 patient) Dizziness (1 patient) Other AEs: Delirium (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69-70
10 mg 2 times / day steady, oral Dose: 10 mg, 2 times / day Route: oral Route: steady Dose: 10 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69
15 mg 2 times / day steady, oral Dose: 15 mg, 2 times / day Route: oral Route: steady Dose: 15 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 70	healthy n = 70 Health Status: healthy Population Size: 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 70	Disc. AE: Transaminases increased... AEs leading to discontinuation/dose reduction: Transaminases increased (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 70
60 mg 2 times / day steady, oral Dose: 60 mg, 2 times / day Route: oral Route: steady Dose: 60 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69
70 mg 2 times / day steady, oral Dose: 70 mg, 2 times / day Route: oral Route: steady Dose: 70 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	healthy n = 24 Health Status: healthy Population Size: 24 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69	Disc. AE: Dizziness, Somnolence... AEs leading to discontinuation/dose reduction: Dizziness (1 patient) Somnolence (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000MedR.pdf Page: p. 69

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 707 substrate 1603 inhibitor 1461	inhibitor 1605	inhibitor 1701	inhibitor 1480

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1386 CYP2C8 818 CYP2C19 1324 UGT1A1 191 UGT1A4 74 UGT1A6 103 UGT2B4 22 P-gp 1344	CYP2C19 911 CYP2B6 616 P-gp 1399 OAT 1	UGT1A1 64

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1532	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2C19 1394	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2C8 868	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2C9 1652	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP3A4 1768	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
P-gp 1519	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0	no
UGT1A1 239	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
UGT1A4 77	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
UGT1A6 135	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
UGT2B4 22	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no
CYP2D6 1735	inhibitor 3041 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0	no	yes (co-administration study) Comment: clobazam increased dextromethorphan cmax 90%, auc 59% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 16.0
UGT1A1 239	inducer 1443 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0	weak
CYP3A4 1768	inducer 1443 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 9.0	weak	yes (co-administration study) Comment: clobazam decreased midazolam auc 27%, cmax 24% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 9.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1603	substrate 3107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0	major	yes (co-administration study) Comment: ketoconazole increased clobazam auc 54%, no effect on cmax Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0
CYP2B6 616	substrate 3107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0	minor
CYP2C19 911	substrate 3107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0	minor	yes (co-administration study) Comment: omeprazole increased clobazam auc 30-36%, no effect on cmax Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 15.0
OAT 1	substrate 3107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000ClinPharmR.pdf Page: 96.0	no
P-gp 1399	substrate 3107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0	yes	yes (co-administration study) Comment: verapamil reduced clobazam transport >96% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202067s000lbl.pdf Page: 17.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1512	inhibitor 1494 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202067Orig1s000CrossR.pdf Page: 20.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31413	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31413
ZINC	ZINC000000001175	http://zinc15.docking.org/substances/ZINC000000001175
eMolecules	536528	https://www.emolecules.com/cgi-bin/more?vid=536528

PubMed

Title	Date	PubMed
Management strategies for refractory localization-related seizures.	2001	11520319
Epileptic encephalopathy.	2001	11520318
[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].	2001 Aug	11530681
[Clinical features and treatment of refractory epilepsy in children].	2001 Dec	12235805
Infantile spasms: diagnosis and assessment of treatment response by video-EEG.	2001 Oct	11665822
Evolution of juvenile myoclonic epilepsy treated from the outset with sodium valproate.	2001 Sep	11700996
Psychosomatic reactions to a stressful environment and an attempt at pharmacological modification.	2001 Sep-Oct	11535941
On the use of tranquillisers in epilepsy.	2002	11903479
Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam.	2002 Dec	12451290
Vagus nerve stimulation in a case of epilepsy with CSWSS: respiratory side effects during sleep.	2002 Oct	12366745
A casuistic rationale for the treatment of spastic and myocloni in a childhood neurodegenerative disease: neuronal ceroid lipofuscinosis of the type Jansky-Bielschowsky.	2002 Oct-Dec	12500158
Direct injection HPLC method for the determination of selected benzodiazepines in plasma using a Hisep column.	2003 Dec 4	14656604
Mechanism-based pharmacokinetic/pharmacodynamic modeling of the electroencephalogram effects of GABAA receptor modulators: in vitro-in vivo correlations.	2003 Jan	12490579
Use of clobazam for the treatment of refractory complex partial seizures.	2003 Jul	12810340
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
Unusual side-effects due to clobazam: a case report with genetic study of CYP2C19.	2004 Jan	14729419
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
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
[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
Intermittent clobazam therapy in febrile seizures.	2005 Jan	15684445
Stiripentol.	2005 Jul	16022579
Neuroembryopathic effect of clobazam in rat: a histological study.	2005 Jun	16295712
Visually self-induced seizures sensitive to round objects.	2005 May	15857450
Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry.	2005 Oct 15	16154525
Levetiracetam in idiopathic generalised epilepsy and porphyria cutanea tarda.	2006	17163270
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
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 `Fri Jun 25 21:15:48 UTC 2021` Edited by `admin` on `Fri Jun 25 21:15:48 UTC 2021`
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

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 [EP MONOGRAPH]

Common Name

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