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Showing drug card for Zopiclone (DB01198)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:05
Primary Accession Number DB01198
Secondary Accession Number
  • APRD00356
Name Zopiclone
Drug Type
  • Approved
  • Small Molecule
Description Zopiclone is a novel hypnotic agent used in the treatment of insomnia. Its mechanism of action is based on modulating benzodiazepine receptors. In addition to zopiclone's benzodiazepine pharmacological properties it also has some barbiturate like properties.
Synonyms
  1. (+-)-zopiclone
  2. Zopiclona [INN-Spanish]
  3. Zopiclone [Ban:Inn:Jan]
  4. Zopiclonum [INN-Latin]
Brand Names
  1. Amoban
  2. Amovane
  3. Imovance
  4. Imovane
  5. Novo-zopiclone
  6. Nu-Zopiclone
  7. Ran-zopiclone
  8. Rhovane
  9. Sopivan
  10. Ximovan
  11. Zimovane
Brand Mixtures Not Available
Chemical IUPAC Name [6-(5-chloropyridin-2-yl)-5-oxo-7H-pyrrolo[3,4-b]pyrazin-7-yl] 4-methylpiperazine-1-carboxylate
Chemical Formula C17H17ClN6O3
Chemical Structure Structure
CAS Registry Number 43200-80-2
InChI Identifier InChI=1/C17H17ClN6O3/c1-22-6-8-23(9-7-22)17(26)27-16-14-13(19-4-5-20-14)15(25)24(16)12-3-2-11(18)10-21-12/h2-5,10,16H,6-9H2,1H3
InChI Key GBBSUAFBMRNDJC-UHFFFAOYAX
KEGG Drug D01372 Link Image
KEGG Compound Not Available
PubChem Compound 5735 Link Image
PubChem Substance 583197 Link Image
ChEBI ID Not Available
PharmGKB ID PA10236 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02257580 Link Image
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Zopiclone Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 388.8080
Monoisotopic Molecular Weight 388.1051
State Solid
Melting Point 178 oC
Experimental Water Solubility 0.151 mg/mL at 25 oC [MEYLAN,WM et al. (1996)] Source: PhysProp
Predicted Water Solubility 8.85e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.8 Source: PhysProp
Predicted LogP 0.97 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.64 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 CN1CCN(CC1)C(=O)O[C@@H]1N(C(=O)C2=NC=CN=C12)C1=NC=C(Cl)C=C1
Canonical SMILES CN1CCN(CC1)C(=O)OC1N(C(=O)C2=NC=CN=C12)C1=NC=C(Cl)C=C1
Drug Category
  • Hypnotics and Sedatives
ATC Codes
AHFS Codes
  • 28:24.92
Indication For the short-term treatment of insomnia.
Pharmacology Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.
Mechanism of Action Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex.
Absorption Rapidly absorbed following oral administration.
Toxicity Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agent. Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing.
Protein Binding Approximately 45%
Biotransformation Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance.
Half Life Elimination half life is approximately 5 hours (range 3.8 to 6.5 hours) and is prolonged to 11.9 hours in patients with hepatic insufficiency.
Dosage Forms
Form Route
Tablet Oral
Tablet Oral
Patient Information Not Available
Contraindications Not Available
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T: Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004 Jul;19(5):305-22. [PubMed Link Image]
  2. Liu HJ, Sato K, Shih HC, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats. Int J Clin Pharmacol Ther Toxicol. 1985 Mar;23(3):121-8. [PubMed Link Image]
  3. Sato K, Hong YL, Yang MS, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):204-10. [PubMed Link Image]
  4. Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM: Pharmacological studies on zopiclone. Pharmacology. 1983;27 Suppl 2:46-58. [PubMed Link Image]
  5. Blanchard JC, Julou L: Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum. J Neurochem. 1983 Mar;40(3):601-7. [PubMed Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C8 (CYP2C8)
Targets
  1. Translocator protein
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C8 (CYP2C8)
Enzyme 1 Gene Name CYP2C8
Enzyme 1 SwissProt ID P10632 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P10632|CP2C8_HUMAN Cytochrome P450 2C8 (EC 1.14.14.1) 
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV
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. 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.