| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:06:36 |
| Primary Accession Number |
DB00349 |
| Secondary Accession Number |
|
| Name |
Clobazam |
| Drug Type |
- Approved
- Illicit
- Investigational
- Small Molecule
|
| Description |
Clobazam is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. [Wikipedia] |
| Synonyms |
- clobazam
|
| Brand Names |
- Chlorepin
- Clorepin
- Frisium
- Mystan
- Urbadan
- Urbanyl
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
8-chloro-5-methyl-1-phenyl-1,5-benzodiazepine-2,4-dione |
| Chemical Formula |
C16H13ClN2O2 |
| Chemical Structure |
 |
| CAS Registry Number |
22316-47-8 |
| InChI Identifier |
InChI=1/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 |
| InChI Key |
CXOXHMZGEKVPMT-UHFFFAOYAS |
| KEGG Drug |
D01253  |
| KEGG Compound |
Not Available |
| PubChem Compound |
2789  |
| PubChem Substance |
583072  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA10888  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02247230  |
| RxList Link |
Not Available |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Clobazam  |
| FDA Label |
Not Available |
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
300.7400 |
| Monoisotopic Molecular Weight |
300.0666 |
| State |
Solid |
| Melting Point |
Not Available |
| Experimental Water Solubility |
188 mg/L
Source: PhysProp
|
| Predicted Water Solubility |
1.64e-01 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
2.3
Source: PhysProp
|
| Predicted LogP |
2.14
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-3.26
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CN1C(=O)CC(=O)N(C2=CC=CC=C2)C2=C1C=CC(Cl)=C2 |
| Canonical SMILES |
CN1C(=O)CC(=O)N(C2=CC=CC=C2)C2=C1C=CC(Cl)=C2 |
| Drug Category |
- Anticonvulsants
- Benzodiazepines
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For treatment and management of epilepsy and anxiety disorder. |
| Pharmacology |
Clobazam is a barbiturate used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. |
| Mechanism of Action |
Clobazam binds at a distinct binding site associated with a Cl- ionopore at the GABA-A receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is prolonged as a result. |
| Absorption |
Bioavailability is 90%. |
| Toxicity |
Not Available |
| Protein Binding |
83% |
| Biotransformation |
Hepatic. Clobazam has two major metabolites: N-desmethyl-clobazam and 4'-hydroxyclobazam, the former of which is active. The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4'-hydroxyclobazam by CYP2C18 and CYP2C19. |
| Half Life |
18 hours |
| Dosage Forms |
|
| Patient Information |
Not Available |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Clozapine |
Increased risk of toxicity |
| Kava |
Kava increases the effect of the benzodiazepine |
|
| Food Interactions |
- Alcohol increases clobazam absorption by 50%.
- Take without regard to meals.
|
| Pathways |
Not Available
|
| General References |
- : 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
]
- 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
]
- Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44. [PubMed
]
- Freche C: [Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations] Sem Hop Ther. 1975 Apr;51(4):261-3. [PubMed
]
- Drugs.com

- Wikipedia

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2C19 (CYP2C19)
|
| Targets |
- Gamma-aminobutyric-acid receptor subunit alpha-1
|
|
Drug Target 1
[top]
|
| Target 1 ID |
872 |
| Target 1 Name |
Gamma-aminobutyric-acid receptor subunit alpha-1 |
| Target 1 Synonyms |
- Gamma-aminobutyric-acid receptor subunit alpha-1 precursor
|
| Target 1 Gene Name |
GABRA1 |
| Target 1 Protein Sequence |
>Gamma-aminobutyric-acid receptor subunit alpha-1 precursor
MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC
PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM
TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP
LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID
RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ
|
| Target 1 Number of Residues |
463 |
| Target 1 Molecular Weight |
51802 |
| Target 1 Theoretical pI |
9.61 |
| Target 1 GO Classification |
|
Function
|
neurotransmitter receptor activity
transporter activity
ion transporter activity
ion channel activity
ligand-gated ion channel activity
extracellular ligand-gated ion channel activity
signal transducer activity
receptor activity
transmembrane receptor activity
GABA receptor activity
GABA-A receptor activity |
|
Process
|
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
gamma-aminobutyric acid signaling pathway
anion transport
inorganic anion transport
chloride transport
physiological process
cellular physiological process
transport
ion transport |
|
Component
|
postsynaptic membrane
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 1 General Function |
Involved in GABA-A receptor activity |
| Target 1 Specific Function |
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 252-273
- 279-300
- 313-334
- 422-443
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
31631  |
| Target 1 UniProtKB/Swiss-Prot ID |
P14867  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
GBRA1_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 1 Gene Sequence |
>1371 bp
ATGAGGAAAAGTCCAGGTCTGTCTGACTGTCTTTGGGCCTGGATCCTCCTTCTGAGCACA
CTGACTGGAAGAAGCTATGGACAGCCGTCATTACAAGATGAACTTAAAGACAATACCACT
GTCTTCACCAGGATTTTGGACAGACTCCTAGATGGTTATGACAATCGCCTGAGACCAGGA
TTGGGAGAGCGTGTAACCGAAGTGAAGACTGATATCTTCGTCACCAGTTTCGGACCCGTT
TCAGACCATGATATGGAATATACAATAGATGTATTTTTCCGTCAAAGCTGGAAGGATGAA
AGGTTAAAATTTAAAGGACCTATGACAGTCCTCCGGTTAAATAACCTAATGGCAAGTAAA
ATCTGGACTCCGGACACATTTTTCCACAATGGAAAGAAGTCAGTGGCCCACAACATGACC
ATGCCCAACAAACTCCTGCGGATCACAGAGGATGGCACCTTGCTGTACACCATGAGGCTG
ACAGTGAGAGCTGAATGTCCGATGCATTTGGAGGACTTCCCTATGGATGCCCATGCTTGC
CCACTAAAATTTGGAAGTTATGCTTATACAAGAGCAGAAGTTGTTTATGAATGGACCAGA
GAGCCAGCACGCTCAGTGGTTGTAGCAGAAGATGGATCACGTCTAAACCAGTATGACCTT
CTTGGACAAACAGTAGACTCTGGAATTGTCCAGTCAAGTACAGGAGAATATGTTGTTATG
ACCACTCATTTCCACTTGAAGAGAAAGATTGGCTACTTTGTTATTCAAACATACCTGCCA
TGCATAATGACAGTGATTCTCTCACAAGTCTCCTTCTGGCTCAACAGAGAGTCTGTACCA
GCAAGAACTGTCTTTGGAGTAACAACTGTGCTCACCATGACAACATTGAGCATCAGTGCC
AGAAACTCCCTCCCTAAGGTGGCTTATGCAACAGCTATGGATTGGTTTATTGCCGTGTGC
TATGCCTTTGTGTTCTCAGCTCTGATTGAGTTTGCCACAGTAAACTATTTCACTAAGAGA
GGTTATGCATGGGATGGCAAAAGTGTGGTTCCAGAAAAGCCAAAGAAAGTAAAGGATCCT
CTTATTAAGAAAAACAACACTTACGCTCCAACAGCAACCAGCTACACCCCTAATTTGGCC
AGGGGCGACCCGGGCTTAGCCACCATTGCTAAAAGTGCAACCATAGAACCTAAAGAGGTC
AAGCCCGAAACAAAACCACCAGAACCCAAGAAAACCTTTAACAGTGTCAGCAAAATTGAC
CGACTGTCAAGAATAGCCTTCCCGCTGCTATTTGGAATCTTTAACTTAGTCTACTGGGCT
ACGTATTTAAACAGAGAGCCTCAGCTAAAAGCCCCCACACCACATCAATAG
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
GABRA1  |
| Target 1 GenAtlas ID |
GABRA1  |
| Target 1 HGNC ID |
HGNC:4075  |
| Target 1 Chromosome Location |
5 |
| Target 1 Locus |
5q34-q35 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Wang YT, Rouleau GA: Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002 Jun;31(2):184-9. Epub 2002 May 6. [PubMed
]
- Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH: Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits. FEBS Lett. 1989 Feb 27;244(2):361-4. [PubMed
]
- Garrett KM, Duman RS, Saito N, Blume AJ, Vitek MP, Tallman JF: Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. Biochem Biophys Res Commun. 1988 Oct 31;156(2):1039-45. [PubMed
]
|
| Target 1 Drug References |
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|