Clobazam
Identification
- Summary
Clobazam is a benzodiazepine used as adjunct treatment in seizures associated with Lennox-Gastaut syndrome.
- Brand Names
- Onfi, Sympazan
- Generic Name
- Clobazam
- DrugBank Accession Number
- DB00349
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
Structure for Clobazam (DB00349)
- Weight
- Average: 300.74
Monoisotopic: 300.066555377 - Chemical Formula
- C16H13ClN2O2
- 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
Pharmacology
- Indication
For treatment and management of epilepsy and seizures associated with Lennox-Gastaut syndrome, a difficult-to-treat form of childhood epilepsy.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - 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 to form two major metabolites, N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, respectively. N-desmethylclobazam (norclobazam) retains pharmacological activity. 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.
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- 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
- Adverse Effects
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The most common adverse effects include somnolence, pyrexia, upper respiratory tract infection, and lethargy.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C19 CYP2C19*2 (A;A) / (A;G) G > A/C ADR Directly Studied Patients with this genotype have reduced metabolism of clobazam. Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A ADR Inferred Clobazem 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 2C19 CYP2C19*2B Not Available 681G>A ADR Inferred Clobazem 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 2C19 CYP2C19*3 Not Available 636G>A ADR Inferred Clobazem 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 2C19 CYP2C19*4 Not Available 1A>G ADR Inferred Clobazem 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 2C19 CYP2C19*5 Not Available 1297C>T ADR Inferred Clobazem 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 2C19 CYP2C19*6 Not Available 395G>A ADR Inferred Clobazem 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 2C19 CYP2C19*7 Not Available 19294T>A ADR Inferred Clobazem 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 2C19 CYP2C19*22 Not Available 557G>C / 991A>G ADR Inferred Clobazem 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 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all ADR Inferred Clobazem 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 2C19 CYP2C19*35 Not Available 12662A>G ADR Inferred Clobazem 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
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Clobazam is combined with 1,2-Benzodiazepine. Abacavir Clobazam may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Clobazam can be increased when it is combined with Abametapir. Abatacept The metabolism of Clobazam can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Clobazam. Abiraterone The metabolism of Clobazam can be decreased when combined with Abiraterone. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Clobazam. Acebutolol The metabolism of Acebutolol can be decreased when combined with Clobazam. Aceclofenac Aceclofenac may decrease the excretion rate of Clobazam which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Clobazam which could result in a higher serum level. 
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- Avoid alcohol. Alcohol increases clobazam absorption by 50%.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- 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)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clobazam-10 Tablet 10 mg Oral Pro Doc Limitee 2003-12-09 2017-05-05 Canada 
Frisium Tab 10mg Tablet 10 mg / tab Oral Hoechst Canada Inc. 1991-12-31 1996-08-29 Canada Frisium Tablet 10mg Tablet 10 mg Oral Lundbeck Pharmaceuticals Llc 1997-03-24 2018-08-31 Canada Frisium Tablets 10mg Tablet 10 mg Oral Hoechst Roussel Canada Inc. 1994-12-31 1999-08-11 Canada Onfi Suspension 2.5 mg/1mL Oral Lundbeck Pharmaceuticals Llc 2012-12-14 Not applicable US 
Onfi Tablet 5 mg/1 Oral Lundbeck Inc. 2011-10-21 2011-10-31 US Onfi Tablet 20 mg/1 Oral Lundbeck Inc. 2011-10-21 2011-10-31 US Onfi Tablet 20 mg/1 Oral Lundbeck Pharmaceuticals Llc 2013-12-10 Not applicable US 
Onfi Tablet 10 mg/1 Oral Lundbeck Inc. 2011-10-21 2011-10-31 US Onfi Tablet 10 mg/1 Oral Lundbeck Pharmaceuticals Llc 2013-12-10 Not applicable US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-clobazam Tablet 10 mg Oral Apotex Corporation 2001-11-28 Not applicable Canada Clobazam Tablet 10 mg/1 Oral Amneal Pharmaceuticals NY LLC 2018-10-22 Not applicable US Clobazam Tablet 20 mg/1 Oral Camber Pharmaceuticals, Inc. 2018-10-22 Not applicable US Clobazam Suspension 2.5 mg/1mL Oral Ascend Laboratories, LLC 2021-05-07 Not applicable US Clobazam Suspension 2.5 mg/1mL Oral Vistapharm, Inc. 2019-08-30 Not applicable US Clobazam Suspension 2.5 mg/1mL Oral Taro Pharmaceuticals U.S.A., Inc. 2021-06-30 Not applicable US Clobazam Tablet 10 mg/1 Oral Cadila Healthcare Limited 2018-10-22 Not applicable US Clobazam Tablet 10 mg/1 Oral Bionpharma Inc. 2017-10-20 Not applicable US Clobazam Suspension 2.5 mg/1mL Oral Mylan Pharmaceuticals Inc. 2018-11-07 Not applicable US Clobazam Tablet 20 mg/1 Oral Lannett Company, Inc. 2019-10-30 Not applicable US
Categories
- ATC Codes
- N05BA09 — Clobazam
- Drug Categories
- Anti-Anxiety Agents
- Anticonvulsants
- Benzazepines
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Agonists
- GABA-A Receptor Agonists
- Heterocyclic Compounds, Fused-Ring
- Nervous System
- Neurotransmitter Agents
- P-glycoprotein substrates
- Psycholeptics
- Psychotropic Drugs
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- 1,3-dicarbonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzodiazepine / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 13 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organochlorine compound, 1,4-benzodiazepinone (CHEBI:31413)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2MRO291B4U
- CAS number
- 22316-47-8
- 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
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
- Freche C: [Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]. Sem Hop Ther. 1975 Apr;51(4):261-3. [Article]
- 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. [Article]
- 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. [Article]
- Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0014493
- KEGG Drug
- D01253
- PubChem Compound
- 2789
- PubChem Substance
- 46506115
- ChemSpider
- 2687
- BindingDB
- 50247888
- 21241
- ChEBI
- 31413
- ChEMBL
- CHEMBL70418
- ZINC
- ZINC000000001175
- Therapeutic Targets Database
- DAP000672
- PharmGKB
- PA10888
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Clobazam
- FDA label
- Download (595 KB)
- MSDS
- Download (57.5 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Anxiety / Epilepsies 1 4 Recruiting Prevention Epilepsy, Intractable / Gliomas, Malignant / Seizures Disorders 1 4 Unknown Status Treatment Epilepsies 2 4 Unknown Status Treatment Refractory Epilepsy 1 3 Completed Basic Science Back Pain Lower Back 1 3 Completed Treatment Epilepsies / Epilepsy, Generalized / Seizures 1 3 Completed Treatment Lennox Gastaut Syndrome (LGS) 1 3 Completed Treatment Pain 1 3 Terminated Treatment Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia 1 3 Terminated Treatment Dravet Syndrome (DS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral 2.5 mg/1mL Suspension Oral 2.5 mg/1mL Suspension Oral Capsule Tablet Oral Tablet Oral 10 mg / tab Tablet Oral 10 mg Tablet Oral 20 mg Tablet Oral 10 mg/1 Tablet Oral 20 mg/1 Tablet Oral 5 mg/1 Film Oral 10 mg/1 Film Oral 20 mg/1 Film Oral 5 mg/1 Suspension Oral 0.25 g - Prices
Unit description Cost Unit Apo-Clobazam 10 mg Tablet 0.23USD tablet Novo-Clobazam 10 mg Tablet 0.23USD tablet Pms-Clobazam 10 mg Tablet 0.23USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8603514 No 2013-12-10 2024-04-03 US US8765167 No 2014-07-01 2024-02-20 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 180-182 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. water solubility 188 mg/L Not Available logP 2.12 HENCZI,M ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.164 mg/mL ALOGPS logP 2.14 ALOGPS logP 2.55 ChemAxon logS -3.3 ALOGPS pKa (Strongest Acidic) 4.07 ChemAxon pKa (Strongest Basic) -6.7 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 40.62 Å2 ChemAxon Rotatable Bond Count 1 ChemAxon Refractivity 80.3 m3·mol-1 ChemAxon Polarizability 30.07 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.99 Blood Brain Barrier + 0.9904 Caco-2 permeable + 0.7487 P-glycoprotein substrate Non-substrate 0.5733 P-glycoprotein inhibitor I Non-inhibitor 0.5462 P-glycoprotein inhibitor II Non-inhibitor 0.9204 Renal organic cation transporter Non-inhibitor 0.7373 CYP450 2C9 substrate Non-substrate 0.7058 CYP450 2D6 substrate Non-substrate 0.8607 CYP450 3A4 substrate Substrate 0.6871 CYP450 1A2 substrate Non-inhibitor 0.6829 CYP450 2C9 inhibitor Non-inhibitor 0.5296 CYP450 2D6 inhibitor Non-inhibitor 0.8908 CYP450 2C19 inhibitor Non-inhibitor 0.5791 CYP450 3A4 inhibitor Inhibitor 0.7008 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5308 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.7846 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.7313 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9896 hERG inhibition (predictor II) Non-inhibitor 0.8651
Spectra
- Mass Spec (NIST)
- Download (11.4 KB)
- Spectra
Targets
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- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- Curator comments
- The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
- 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
- Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [Article]
- 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. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- Curator comments
- Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
- 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
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- 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
- 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. [Article]
- de Leon J, Spina E, Diaz FJ: Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013 Feb;35(1):30-47. doi: 10.1097/FTD.0b013e31827ada88. [Article]
- Huddart R, Leeder JS, Altman RB, Klein TE: PharmGKB summary: clobazam pathway, pharmacokinetics. Pharmacogenet Genomics. 2018 Apr;28(4):110-115. doi: 10.1097/FPC.0000000000000327. [Article]
- Clobazam FDA label [Link]
- Kind
- Protein
- Organism
- Humans
- 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
- de Leon J, Spina E, Diaz FJ: Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013 Feb;35(1):30-47. doi: 10.1097/FTD.0b013e31827ada88. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Tolbert D, Larsen F: A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019 Jan;59(1):7-19. doi: 10.1002/jcph.1313. Epub 2018 Oct 4. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
References
- Huddart R, Leeder JS, Altman RB, Klein TE: PharmGKB summary: clobazam pathway, pharmacokinetics. Pharmacogenet Genomics. 2018 Apr;28(4):110-115. doi: 10.1097/FPC.0000000000000327. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- 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 13:24 / Updated on October 19, 2021 07:39