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Record Information
Version2.0
Creation Date2009-07-21 20:28:36 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3016
Identification
Common NameZopiclone
ClassSmall Molecule
DescriptionZopiclone is only found in individuals that have used or taken this drug. It 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. Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α1, α2, α3 and α5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.
Compound Type
  • Amide
  • Amine
  • Drug
  • Ester
  • Ether
  • Hypnotic and Sedative
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+-)-zopiclone
(±)-zopiclone
6-(5-Chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methyl-1-piperazinecarboxylate
Amoban
Imovane
Rhovane
Zimovane
Zopiclona
Zopiclonum
Chemical FormulaC17H17ClN6O3
Average Molecular Mass388.808 g/mol
Monoisotopic Mass388.105 g/mol
CAS Registry Number43200-80-2
IUPAC Name6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
Traditional Namezopiclone
SMILESCN1CCN(CC1)C(=O)OC1N(C(=O)C2=C1N=CC=N2)C1=NC=C(Cl)C=C1
InChI IdentifierInChI=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 KeyInChIKey=GBBSUAFBMRNDJC-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cyclopyrrolones. Cyclopyrrolones are compounds belonging to a family of pyridin-2-ylpyrrole based chemicals. The pyrrole is usually fused to a benzene, pyrimidine, or dithiin.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrrolopyrazines
Sub ClassCyclopyrrolones
Direct ParentCyclopyrrolones
Alternative Parents
Substituents
  • Cyclopyrrolone
  • Piperazine-1-carboxylic acid
  • 2-heteroaryl carboxamide
  • N-methylpiperazine
  • N-alkylpiperazine
  • Aryl chloride
  • Aryl halide
  • Imidolactam
  • Pyridine
  • Pyrazine
  • Piperazine
  • 1,4-diazinane
  • Heteroaromatic compound
  • Carbamic acid ester
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Carboxamide group
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Carbonic acid derivative
  • Azacycle
  • Carboxylic acid derivative
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organic oxide
  • Amine
  • Carbonyl group
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organohalogen compound
  • Organochloride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point178°C
Boiling PointNot Available
Solubility0.151 mg/mL at 25°C
LogP0.8
Predicted Properties
PropertyValueSource
Water Solubility0.885 mg/mLALOGPS
logP0.97ALOGPS
logP0.81ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)13.04ChemAxon
pKa (Strongest Basic)6.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area91.76 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity95.89 m3·mol-1ChemAxon
Polarizability37.67 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-05bb-9212000000-b3e4c2874ff86d2544e1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00kb-0090000000-9d80e08080f406848221View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0092000000-977d45f9a516242be80fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0090000000-397a508c11f66c161327View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014j-0090000000-abc6a676659114a83d08View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014i-0790000000-74d7c73e854e61700433View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00lr-0920000000-2c17f6282d1031cb4d50View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-c0f92aba9374337ff737View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-003r-5900000000-46755df8b5cfb7f46bf9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-9300000000-091d5434bc674d5bf9a4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-9000000000-87365fa01fb0854897caView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-58198ad5b8e6fb5075fcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-5917000000-fed7a3a68ceccd2f26beView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ac0-9000000000-ef1623aed48bd5073d7bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0309000000-e2a958d8569e44198c06View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1901000000-d74484c0d625330ab7cdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-9510000000-15dec99e5a9537957558View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0007-6950000000-c1583a92e3cbc5066186View in MoNA
1D NMR13C NMR SpectrumNot Available
Toxicity Profile
Route of ExposureRapidly absorbed following oral administration.
Mechanism of ToxicityZopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on alpha1, alpha2, alpha3 and alpha5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.
MetabolismExtensively 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.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the short-term treatment of insomnia.
Minimum Risk LevelNot Available
Health EffectsThey cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.
SymptomsRare 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.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01198
HMDB IDHMDB15329
PubChem Compound ID5735
ChEMBL IDCHEMBL135400
ChemSpider ID5533
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID32315
BioCyc IDNot Available
CTD IDNot Available
Stitch IDZopiclone
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkZopiclone
References
Synthesis Reference

Thomas Jerussi, “Compositions comprising zopiclone derivatives and methods of making and using the same.” U.S. Patent US20040147521, issued July 29, 2004.

MSDST3D3016.pdf
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. [15252823 ]
  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. [2581904 ]
  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. [2860074 ]
  4. 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. [6298365 ]
  5. Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM: Pharmacological studies on zopiclone. Pharmacology. 1983;27 Suppl 2:46-58. [6142468 ]
  6. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
  3. Sanger DJ: The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents. CNS Drugs. 2004;18 Suppl 1:9-15; discussion 41, 43-5. [15291009 ]
  4. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [6135616 ]
  5. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [20303942 ]
General Function:
Transporter activity
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.
Gene Name:
GABRA5
Uniprot ID:
P31644
Molecular Weight:
52145.645 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
  3. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [6135616 ]
  4. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [20303942 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
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.
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular Weight:
51325.85 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
  3. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [20303942 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
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.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [19942638 ]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [18973287 ]
  3. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [20303942 ]
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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. [17016423 ]