Identification

Name
Clobazam
Accession Number
DB00349  (APRD00307)
Type
Small Molecule
Groups
Approved, Illicit
Description

Clobazam 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.

Structure
Thumb
Synonyms
  • 1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepine
  • 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione
  • Clobazam
  • Clobazamum
External IDs
H 4723 / H-4723 / HR 376 / HR-376 / LM 2717 / LM-2717
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clobazam-10Tablet10 mgOralPro Doc Limitee2003-12-09Not applicableCanada
Frisium Tab 10mgTablet10 mgOralHoechst Canada Inc.1991-12-311996-08-29Canada
Frisium Tablet 10mgTablet10 mgOralLundbeck Inc.1997-03-24Not applicableCanada
Frisium Tablets 10mgTablet10 mgOralHoechst Roussel Canada Inc.1994-12-311999-08-11Canada
OnfiTablet10 mg/1OralLundbeck Inc.2011-10-212011-10-31Us
OnfiTablet20 mg/1OralLundbeck Pharmaceuticals Llc2013-12-10Not applicableUs67386 0315 01 nlmimage10 123f892c
OnfiTablet5 mg/1OralLundbeck Inc.2011-10-212011-10-31Us
OnfiTablet10 mg/1OralLundbeck Pharmaceuticals Llc2013-12-10Not applicableUs67386 0314 01 nlmimage10 173f8b9c
OnfiTablet20 mg/1OralLundbeck Inc.2011-10-212011-10-31Us
OnfiSuspension2.5 mg/1mLOralLundbeck Pharmaceuticals Llc2012-12-14Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-clobazamTablet10 mgOralApotex Corporation2001-11-28Not applicableCanada
Dom-clobazamTablet10 mgOralDominion Pharmacal2003-03-272016-10-25Canada
Ntp-clobazamTablet10 mgOralTevaNot applicableNot applicableCanada
PMS-clobazamTablet10 mgOralPharmascience Inc2001-11-16Not applicableCanada
Ratio-clobazamTablet10 mgOralRatiopharm Inc Division Of Teva Canada Limited1998-11-302010-08-02Canada
Teva-clobazamTablet10 mgOralTeva1998-07-07Not applicableCanada
International/Other Brands
Aedon (Sanofi-Aventis) / Castilium (Sanofi-Aventis) / Clobam (Square) / Clobamax (Sherfarma) / Frisium (Sanofi-Aventis) / Grifoclobam (Chile) / Mystan (Dainippon Sumitomo) / Noiafren (Sanofi Aventis) / Sederlona / Urbanil (Sanofi-Aventis) / Urbanol (Sanofi-Aventis) / Urbanyl (Sanofi-Aventis) / Venium (Hudson)
Categories
UNII
2MRO291B4U
CAS number
22316-47-8
Weight
Average: 300.74
Monoisotopic: 300.066555377
Chemical Formula
C16H13ClN2O2
InChI Key
CXOXHMZGEKVPMT-UHFFFAOYSA-N
InChI
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
IUPAC Name
7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione
SMILES
CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O

Pharmacology

Indication

For treatment and management of epilepsy and seizures associated with Lennox-Gastaut syndrome, a difficult-to-treat form of childhood epilepsy.

Associated Conditions
Pharmacodynamics

Similar to other benzodiazepines, clobazam binds to the interface of the α and γ2-subunit of the GABA-A receptor. However, it is considered a partial agonist to GABA-A receptors which sets clobazam apart from 1,4-benzodiazepines which are full agonist. The significance of this difference is that one may experience less sedation with clobazam than with other benzodiazepines. Unlike the endogenous GABA ligand, clobazam binds allosterically to the GABA receptor to increase the frequency of the chloride channel opening and membrane permeability to chloride ions. Pharmacodynamic tolerance has been demonstrated in animal models.

Mechanism of action

Clobazam 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.

TargetActionsOrganism
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
Absorption

After 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.

Volume of distribution

Vdss = 100 L. This high volume of distribution suggests extensive distribution to body tissues.

Protein binding

Clobazam is the primary circulating entity in the serum and is highly protein-bound (80-90%).

Metabolism

Clobazam 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.

Clearance

Median estimated clearance = 2.49 L/h

Toxicity

The most common adverse effects include somnolence, pyrexia, upper respiratory tract infection, and lethargy.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYP2C19*2(A;A) / (A;G)G > A/CADR Directly StudiedPatients with this genotype have reduced metabolism of clobazam.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all ADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GADR InferredClobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Clobazam.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Clobazam.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be increased when combined with Clobazam.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Clobazam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Clobazam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Clobazam is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Clobazam.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Clobazam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Clobazam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Clobazam is combined with 4-Methoxyamphetamine.
Food Interactions
  • Alcohol increases clobazam absorption by 50%.
  • Take without regard to meals.

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.

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. [PubMed:5777]
  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. [PubMed:2044502]
  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. [PubMed:2106335]
  4. Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44. [PubMed:3117456]
  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. [PubMed:22242724]
  6. 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. [PubMed:23034582]
  7. 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. [PubMed:22422635]
External Links
Human Metabolome Database
HMDB0014493
KEGG Drug
D01253
PubChem Compound
2789
PubChem Substance
46506115
ChemSpider
2687
ChEBI
31413
ChEMBL
CHEMBL70418
Therapeutic Targets Database
DAP000672
PharmGKB
PA10888
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clobazam
ATC Codes
N05BA09 — Clobazam
AHFS Codes
  • 28:12.08 — Benzodiazepines
FDA label
Download (595 KB)
MSDS
Download (57.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedBasic SciencePain, Neuropathic1
2CompletedOtherEpilepsies1
2CompletedTreatmentEpilepsies1
2CompletedTreatmentEpilepsies / Epilepsy, Generalized / Seizures1
3CompletedBasic ScienceLow Back Pain (LBP)1
3CompletedTreatmentEpilepsies / Epilepsy, Generalized / Seizures1
3CompletedTreatmentLennox-Gastaut Syndrome (LGS)1
3CompletedTreatmentPain1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentDravet Syndrome1
3TerminatedTreatmentEpilepsia Partialis Continua / Epilepsies / Kojewnikov's Epilepsy1
3WithdrawnTreatmentDravet Syndrome1
4Active Not RecruitingTreatmentRefractory Epilepsy1
4RecruitingTreatmentEpilepsies2
4RecruitingTreatmentEpilepsies / Feeling Anxious1
Not AvailableRecruitingNot AvailableEpilepsies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral10 mg
SuspensionOral2.5 mg/1mL
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Apo-Clobazam 10 mg Tablet0.23USD tablet
Novo-Clobazam 10 mg Tablet0.23USD tablet
Pms-Clobazam 10 mg Tablet0.23USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180-182Hauptmann, 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.
water solubility188 mg/LNot Available
logP2.12HENCZI,M ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.164 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity80.3 m3·mol-1ChemAxon
Polarizability30.07 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.99
Blood Brain Barrier+0.9904
Caco-2 permeable+0.7487
P-glycoprotein substrateNon-substrate0.5733
P-glycoprotein inhibitor INon-inhibitor0.5462
P-glycoprotein inhibitor IINon-inhibitor0.9204
Renal organic cation transporterNon-inhibitor0.7373
CYP450 2C9 substrateNon-substrate0.7058
CYP450 2D6 substrateNon-substrate0.8607
CYP450 3A4 substrateSubstrate0.6871
CYP450 1A2 substrateNon-inhibitor0.6829
CYP450 2C9 inhibitorNon-inhibitor0.5296
CYP450 2D6 inhibitorNon-inhibitor0.8908
CYP450 2C19 inhibitorNon-inhibitor0.5791
CYP450 3A4 inhibitorInhibitor0.7008
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5308
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7846
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.7313 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9896
hERG inhibition (predictor II)Non-inhibitor0.8651
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11.4 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0pb9-6392000000-a76f30f353b3407df0c6
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0090000000-3b46d60abcc8dfacf4d8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0019000000-71512d7a18cf60430dd9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0092000000-e687a1e3760fb870dbc9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0090000000-d450ded1f22039f00b63
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ab9-0190000000-e4211cbc2957a587e3d3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fr-0590000000-51f4fa0445c2d047ef6b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0g4j-1960000000-a89e1c91bfa7b974be48
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014j-4920000000-93c0877b3acf519d2b98
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-016u-7900000000-bc29714be08b6ae4120b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0hi6-9600000000-7c6a3974d95a0015757e

Taxonomy

Description
This compound 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).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
Not Available
Direct Parent
Benzodiazepines
Alternative Parents
1,4-diazepines / Benzene and substituted derivatives / Aryl chlorides / 1,3-dicarbonyl compounds / Tertiary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides
show 2 more
Substituents
Benzodiazepine / Para-diazepine / Aryl chloride / Aryl halide / Monocyclic benzene moiety / 1,3-dicarbonyl compound / Benzenoid / Tertiary carboxylic acid amide / Lactam / Carboxamide group
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, 1,4-benzodiazepinone (CHEBI:31413)

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [PubMed:15483195]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Other
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A1
Uniprot ID
P30531
Uniprot Name
Sodium- and chloride-dependent GABA transporter 1
Molecular Weight
67073.0 Da
References
  1. 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. [PubMed:22242724]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Other
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A11
Uniprot ID
P48066
Uniprot Name
Sodium- and chloride-dependent GABA transporter 3
Molecular Weight
70605.145 Da
References
  1. 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. [PubMed:22242724]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:25