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Showing drug card for Estazolam (DB01215)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:41
Primary Accession Number DB01215
Secondary Accession Number
  • APRD00955
Name Estazolam
Drug Type
  • Approved
  • Illicit
  • Small Molecule
Description A benzodiazepine with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. [PubChem]
Synonyms Not Available
Brand Names
  1. Cannoc
  2. D 40TA
  3. Esilgan
  4. Eurodin
  5. Julodin
  6. Nemurel
  7. Nuctalon
  8. ProSom
  9. Somnatrol
Brand Mixtures Not Available
Chemical IUPAC Name 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Chemical Formula C16H11ClN4
Chemical Structure Structure
CAS Registry Number 29975-16-4
InChI Identifier InChI=1/C16H11ClN4/c17-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)18-9-15-20-19-10-21(14)15/h1-8,10H,9H2
InChI Key CDCHDCWJMGXXRH-UHFFFAOYAH
KEGG Drug D00311 Link Image
KEGG Compound Not Available
PubChem Compound 3261 Link Image
PubChem Substance 9195 Link Image
ChEBI ID Not Available
PharmGKB ID PA449502 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02016060 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/estaz.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/pro1359.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Estazolam Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 294.7380
Monoisotopic Molecular Weight 294.0672
State Solid
Melting Point 228.5 oC
Experimental Water Solubility Practically insoluble (1.5 mg/L) Source: PhysProp
Predicted Water Solubility 4.23e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4.7 Source: PhysProp
Predicted LogP 1.73 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.84 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 ClC1=CC2=C(C=C1)N1C=NN=C1CN=C2C1=CC=CC=C1
Canonical SMILES ClC1=CC2=C(C=C1)N1C=NN=C1CN=C2C1=CC=CC=C1
Drug Category
  • Anti-anxiety Agents
  • Anticonvulsants
  • GABA Modulators
ATC Codes
AHFS Codes Not Available
Indication For the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings.
Pharmacology Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam.
Mechanism of Action Benzodiazepines bind nonspecifically to benzodiazepine receptors, 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 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 Tablets have been found to be equivalent in absorption to an orally administered solution of estazolam. In healthy subjects who received up to three times the recommended dose, peak estazolam plasma concentrations occurred within two hours after dosing (range 0.5 to 6.0 hours) and were proportional to the administered dose, suggesting linear pharmacokinetics over the dosage range tested.
Toxicity Symptoms of overdose include confusion, depressed breathing, drowsiness and eventually coma, lack of coordination, and slurred speech.
Protein Binding 93% protein bound, independant of concentration.
Biotransformation Extensively metabolized in the liver. In vitro studies with human liver microsomes indicate that the biotransformation of estazolam to the major circulating metabolite 4-hydroxy-estazolam is mediated by cytochrome P450 3A (CYP3A).
Half Life The range of estimates for the mean elimination half-life of estazolam varies from 10 to 24 hours.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
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
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. Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5. [PubMed Link Image]
  2. Oishi R, Nishibori M, Itoh Y, Saeki K: Diazepam-induced decrease in histamine turnover in mouse brain. Eur J Pharmacol. 1986 May 27;124(3):337-42. [PubMed Link Image]
  3. Watanabe S, Ohta H, Sakurai Y, Takao K, Ueki S: [Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants] Nippon Yakurigaku Zasshi. 1986 Jul;88(1):19-32. [PubMed Link Image]
  4. Wikipedia Link Image
  5. RxList Link Image
  6. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Translocator protein
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
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. Taketani S, Kohno H, Okuda M, Furukawa T, Tokunaga R: Induction of peripheral-type benzodiazepine receptors during differentiation of mouse erythroleukemia cells. A possible involvement of these receptors in heme biosynthesis. J Biol Chem. 1994 Mar 11;269(10):7527-31. [PubMed Link Image]

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