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Showing drug card for Clorazepate (DB00628)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:56
Primary Accession Number DB00628
Secondary Accession Number
  • APRD00881
Name Clorazepate
Drug Type
  • Approved
  • Illicit
  • Small Molecule
Description A water-soluble benzodiazepine derivative effective in the treatment of anxiety. It has also muscle relaxant and anticonvulsant actions. [PubChem]
Synonyms Not Available
Brand Names
  1. Chlorazepate
  2. Chlorazepic acid
  3. Clorazepate dipotassium
  4. Clorazepic acid
  5. Clorazepic acid [BAN]
  6. Gen-xene
  7. Tranxene
Brand Mixtures Not Available
Chemical IUPAC Name 7-chloro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepine-3-carboxylic acid
Chemical Formula C16H11ClN2O3
Chemical Structure Structure
CAS Registry Number 23887-31-2
InChI Identifier InChI=1/C16H11ClN2O3/c17-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)19-14(16(21)22)15(20)18-12/h1-8,14H,(H,18,20)(H,21,22)/f/h18,21H
InChI Key XDDJGVMJFWAHJX-VUEOKQGPCX
KEGG Drug D00694 Link Image
KEGG Compound Not Available
PubChem Compound 2809 Link Image
PubChem Substance 9138 Link Image
ChEBI ID Not Available
PharmGKB ID PA449056 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00628190 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/clorazepate.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Clorazepate Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 314.7230
Monoisotopic Molecular Weight 314.0458
State Solid
Melting Point Not Available
Experimental Water Solubility Very soluble Source: PhysProp
Predicted Water Solubility 2.48e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3 Source: PhysProp
Predicted LogP 2.68 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.10 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES OC(=O)[C@H]1N=C(C2=CC=CC=C2)C2=C(NC1=O)C=CC(Cl)=C2
Canonical SMILES OC(=O)C1N=C(C2=CC=CC=C2)C2=C(NC1=O)C=CC(Cl)=C2
Drug Category
  • Anti-anxiety Agents
  • Anticonvulsants
  • GABA Modulators
ATC Codes
AHFS Codes
  • 28:24.08
Indication For the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Also used as adjunctive therapy in the management of partial seizures and for the symptomatic relief of acute alcohol withdrawal.
Pharmacology Clorazepate is a member of the group of drugs called benzodiazepines. Pharmacologically, clorazepate has the characteristics of the benzodiazepines. It has depressant effects on the central nervous system. The primary metabolite, nordiazepam, quickly appears in the blood stream. Studies in healthy men have shown that clorazenate has depressant effects on the central nervous system. Since orally administered clorazepate dipotassium is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug.
Mechanism of Action Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
Absorption Rapidly absorbed following oral administration (bioavailability is 91%).
Toxicity Oral LD50 in rats is 1320 mg/kg. In monkeys, oral LD50 exceed 1600 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
Protein Binding The protein binding of nordiazepam in plasma is high (97-98%).
Biotransformation The drug is metabolized in the liver and excreted primarily in the urine. The primary metabolite, nordiazepam, is further metabolized by hydroxylation. The major urinary metabolite is conjugated oxazepam (3-hydroxynordiazepam), and smaller amounts of conjugated p-hydroxynordiazepam and nordiazepam are also found in the urine.
Half Life The serum half-life is about 2 days. Nordiazepam, the primary metabolite, quickly appears in the blood and is eliminated from the plasma with an apparent half-life of about 40 to 50 hours.
Dosage Forms
Form Route
Capsule Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Amprenavir Amprenavir increases the effect and toxicity of benzodiazepine
Cimetidine Cimetidine increases the effect of the benzodiazepine
Clozapine Increased risk of toxicity
Ethotoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Fluconazole Fluconazole increases the effect of the benzodiazepine
Fosamprenavir Amprenavir increases the effect and toxicity of benzodiazepine
Fosphenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Indinavir The protease inhibitor increases the effect of the benzodiazepine
Itraconazole The imidazole increases the effect of the benzodiazepine
Kava Kava increases the effect of the benzodiazepine
Ketoconazole The imidazole increases the effect of the benzodiazepine
Mephenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Nelfinavir The protease inhibitor increases the effect of the benzodiazepine
Omeprazole Omeprazole increases the effect of benzodiazepine
Phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine
Ritonavir The protease inhibitor increases the effect of the benzodiazepine
Saquinavir The protease inhibitor increases the effect of the benzodiazepine
Voriconazole The imidazole increases the effect of the benzodiazepine
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Pathways Not Available
General References
  1. : Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. Br Med J. 1980 Mar 29;280(6218):910-2. [PubMed Link Image]
  2. McElhatton PR: The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994 Nov-Dec;8(6):461-75. [PubMed Link Image]
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Translocator protein
  2. Gamma-aminobutyric-acid receptor subunit alpha-1
Drug Target 1 [top]
Target 1 ID 811
Target 1 Name Translocator protein
Target 1 Synonyms
  1. Mitochondrial benzodiazepine receptor
  2. PBR
  3. PKBS
  4. Peripheral-type benzodiazepine receptor
Target 1 Gene Name BZRP
Target 1 Protein Sequence >Peripheral-type benzodiazepine receptor 
MAPPWVPAMGFTLAPSLGCFVGSRFVHGEGLRWYAGLQKPSWHPPHWVLGPVWGTLYSAM
GYGSYLVWKELGGFTEKAVVPLGLYTGQLALNWAWPPIFFGARQMGWALVDLLLVSGAAA
ATTVAWYQVSPLAARLLYPYLAWLAFATTLNYCVWRDNHGWHGGRRLPE
Target 1 Number of Residues 171
Target 1 Molecular Weight 18779
Target 1 Theoretical pI 9.33
Target 1 GO Classification
Function
Not Available
Process
Not Available
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Signal transduction mechanisms
Target 1 Specific Function Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 6-26
  • 47-67
  • 80-100
  • 106-126
  • 135-155
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 306883 Link Image
Target 1 UniProtKB/Swiss-Prot ID P30536 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name BZRP_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Mitochondrion
  • mitochondrial membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >510 bp 
ATGGCCCCGCCCTGGGTGCCCGCCATGGGCTTCACGCTGGCGCCCAGCCTGGGGTGCTTC
GTGGGCTCCCGCTTTGTCCACGGCGAGGGTCTCCGCTGGTACGCCGGCCTGCAGAAGCCC
TCGTGGCACCCGCCCCACTGGGTGCTGGGCCCTGTCTGGGGCACGCTCTACTCAGCCATG
GGGTACGGCTCCTACCTGGTCTGGAAAGAGCTGGGAGGCTTCACAGAGAAGGCTGTGGTT
CCCCTGGGCCTCTACACTGGGCAGCTGGCCCTGAACTGGGCATGGCCCCCCATCTTCTTT
GGTGCCCGACAAATGGGCTGGGCCTTGGTGGATCTCCTGCTGGTCAGTGGGGCGGCGGCN
GCCACTACCGTGGCCTGGTACCAGGTGAGCCCGCTGGCCGCCCGCCTGCTCTACCCCTAC
CTGGCCTGGCTGGCCTTCGCGACCACACTCAACTACTGCGTATGGCGGGACAACCATGGC
TGGCATGGGGGACGGCGGCTGCCAGAGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID TSPO Link Image
Target 1 GenAtlas ID TSPO Link Image
Target 1 HGNC ID HGNC:1158 Link Image
Target 1 Chromosome Location 22
Target 1 Locus 22q13.31
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed Link Image]
  2. Kurumaji A, Nomoto H, Yoshikawa T, Okubo Y, Toru M: An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample. J Neural Transm. 2000;107(4):491-500. [PubMed Link Image]
  3. Kurumaji A, Nomoto H, Yamada K, Yoshikawa T, Toru M: No association of two missense variations of the benzodiazepine receptor (peripheral) gene and mood disorders in a Japanese sample. Am J Med Genet. 2001 Mar 8;105(2):172-5. [PubMed Link Image]
  4. Riond J, Mattei MG, Kaghad M, Dumont X, Guillemot JC, Le Fur G, Caput D, Ferrara P: Molecular cloning and chromosomal localization of a human peripheral-type benzodiazepine receptor. Eur J Biochem. 1991 Jan 30;195(2):305-11. [PubMed Link Image]
  5. Yakovlev AG, Ruffo M, Jurka J, Krueger KE: Comparison of repetitive elements in the third intron of human and rodent mitochondrial benzodiazepine receptor-encoding genes. Gene. 1995 Apr 3;155(2):201-5. [PubMed Link Image]
  6. Galiegue S, Jbilo O, Combes T, Bribes E, Carayon P, Le Fur G, Casellas P: Cloning and characterization of PRAX-1. A new protein that specifically interacts with the peripheral benzodiazepine receptor. J Biol Chem. 1999 Jan 29;274(5):2938-52. [PubMed Link Image]
Target 1 Drug References
  1. Park CH, Carboni E, Wood PL, Gee KW: Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line. Glia. 1996 Jan;16(1):65-70. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 872
Target 2 Name Gamma-aminobutyric-acid receptor subunit alpha-1
Target 2 Synonyms
  1. Gamma-aminobutyric-acid receptor subunit alpha-1 precursor
Target 2 Gene Name GABRA1
Target 2 Protein Sequence >Gamma-aminobutyric-acid receptor subunit alpha-1 precursor 
MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC
PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM
TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP
LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID
RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ
Target 2 Number of Residues 463
Target 2 Molecular Weight 51802
Target 2 Theoretical pI 9.61
Target 2 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 2 General Function Involved in GABA-A receptor activity
Target 2 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 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-27
Target 2 Transmembrane Regions
  • 252-273
  • 279-300
  • 313-334
  • 422-443
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 31631 Link Image
Target 2 UniProtKB/Swiss-Prot ID P14867 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name GBRA1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 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 2 GenBank Gene ID
Target 2 GeneCard ID GABRA1 Link Image
Target 2 GenAtlas ID GABRA1 Link Image
Target 2 HGNC ID HGNC:4075 Link Image
Target 2 Chromosome Location 5
Target 2 Locus 5q34-q35
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
Target 2 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.