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Details

Stereochemistry RACEMIC
Molecular Formula C17H17ClN6O3
Molecular Weight 388.808
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZOPICLONE

SMILES

CN1CCN(CC1)C(=O)OC2N(C(=O)C3=C2N=CC=N3)C4=CC=C(Cl)C=N4

InChI

InChIKey=GBBSUAFBMRNDJC-UHFFFAOYSA-N
InChI=1S/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

HIDE SMILES / InChI

Description

Zopiclone (brand names Zimovane and Imovane) is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia. The therapeutic pharmacological properties of zopiclone include hypnotic, anxiolytic, anticonvulsant, and myorelaxant properties. Zopiclone and benzodiazepines bind to different sites on GABAA-containing receptors, causing an enhancement of the actions of GABA to produce the therapeutic and adverse effects of zopiclone. The metabolite of zopiclone called desmethylzopiclone is also pharmacologically active, although it has predominately anxiolytic properties. One study found some slight selectivity for zopiclone on α1 and α5 subunits, although it is regarded as being unselective in its binding to α1, α2, α3, and α5 GABAA benzodiazepine receptor complexes. Desmethylzopiclone has been found to have partial agonist properties, unlike the parent drug zopiclone, which is a full agonist. The mechanism of action of zopiclone is similar to benzodiazepines, with similar effects on locomotor activity and on dopamine and serotonin turnover. A meta-analysis of randomised controlled clinical trials that compared benzodiazepines to zopiclone or other Z drugs such as zolpidem and zaleplon has found few clear and consistent differences between zopiclone and the benzodiazepines in sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia, and daytime alertness. After oral administration, zopiclone is rapidly absorbed, with a bioavailability around 75–80%. Time to peak plasma concentration is 1–2 hours. High-fat meal preceding zopiclone administration does not change absorption (as measured by AUC), but reduces peak plasma levels and delays its occurrence, thus may delay the onset of therapeutic effects. The pharmacokinetics of zopiclone in humans are stereoselective. After oral administration of the racemic mixture, Cmax (time to maximum plasma concentration), area under the plasma time-concentration curve (AUC) and terminal elimination half-life values are higher for the dextrorotatory enantiomers, owing to the slower total clearance and smaller volume of distribution (corrected by the bioavailability), compared with the levorotatory enantiomer. In urine, the concentrations of the dextrorotatory enantiomers of the N-dimethyl and N-oxide metabolites are higher than those of the respective antipodes. Zopiclone is sometimes used as a method of suicide. It has a similar fatality index to that of benzodiazepine drugs, apart from temazepam, which is particularly toxic in overdose.

CNS Activity

Originator

Target Info

Target Info

Primary TargetPharmacologyConditionPotency
29.0 nM [IC50]
Condition Info

Condition Info

ConditionModalityTargetsHighest PhaseProduct
Primary
LUNESTA
PMID

PMID

TitleDatePMID
Pharmacological studies on zopiclone.
1983
Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum.
1983 Mar
Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition.
1985 Apr
Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats.
1985 Mar
Subjective effects during administration and on discontinuation of zopiclone and temazepam in normal subjects.
1987 Mar
[First-degree heart block caused by voluntary zopiclone poisoning].
1990 Mar-Apr
[Development of drug withdrawal delirium after dependence on zolpidem and zoplicone].
1999 Nov
Bupropion treatment-related sexual side effects: a case report.
2000 Mar
A possible association between high normal and high dose olanzapine and prolongation of the PR interval.
2002 Jun
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Effects on postural oscillation and memory functions of a single dose of zolpidem 5 mg, zopiclone 3.75 mg and lormetazepam 1 mg in elderly healthy subjects. A randomized, cross-over, double-blind study versus placebo.
2003 Jul
Zopiclone-induced acute interstitial nephritis.
2003 May
Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis.
2004 Jul
Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring.
2005 Oct
Dasatinib-induced acute hepatitis.
2008 Aug
Patent

Patent

Sample Use Guides

In Vivo Use Guide
Oral, 5 mg to 7.5 mg at bedtime.
Route of Administration: Oral
In Vitro Use Guide
To study the effects of Zopiclone , GABA currents were repeatedly elicited by puffer application of 3 mkM GABA every 12 s, and test substances were applied by bath perfusion. A pressurized (10 p.s.i.) puffer pipette (~2 mkm tip diameter) was positioned near the recorded cell, and GABA (3 mkM) was applied by opening a computer-controlled solenoid valve (50–100 ms). This activated a peak inward current (200–2000 pA) that rapidly decayed. Because the small volume of GABA released from the puffer pipette was rapidly diluted in the external bath, the neurons were exposed to a maximum concentration of <3 mkM GABA. This is less than the EC50 of GABA for native and cloned GABAA receptors and provided a reliable starting point to measure potentiation of the current by positive allosteric modulators. Drugs were applied for 3 min (15 evoked GABA currents), which was sufficient for an equilibrium response to be established. Drugs were washed out for at least 3 min. If the GABA current recovered to predrug control amplitude, a higher concentration of drug was applied
Name Type Language
ZOPICLONE
EP   INN   JAN   MART.   MI   WHO-DD  
INN  
Official Name English
6-(5-CHLOROPYRID-2-YL)-5-(4-METHYLPIPERAZIN-1-YL)CARBONYLOXY-7-OXO-6,7-DIHYDRO-5H-PYRROLO(3,4-B)PYRAZINE
Systematic Name English
ZOPICLONE [EP]
Common Name English
ZOPICLONE [MART.]
Common Name English
IMOVANE
Common Name English
AMOBAN
Brand Name English
ZOPICLONE [JAN]
Common Name English
ZOPICLONE [MI]
Common Name English
ZOPICLONE [WHO-DD]
Common Name English
ZIMOVANE
Brand Name English
4-METHYL-1-PIPERAZINECARBOXYLIC ACID ESTER WITH 6-(5-CHLORO-2-PYRIDYL)-6,7-DIHYDRO-7-HYDROXY-5H-PYRROLO(3,4-B)PYRAZIN-5-ONE
Common Name English
RP 27267
Code English
RP-27267
Code English
4-METHYL-1-PIPERAZINECARBOXYLIC ACID 6-(5-CHLORO-2-PYRIDINYL)-6,7-DIHYDRO-7-OXO-5H-PYRROLO(3,4-B)PYRAZIN-5-YL ESTER
Systematic Name English
ZOPICLONE [INN]
Common Name English
Classification Tree Code System Code
DEA NO. 2784
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
WHO-VATC QN05CF01
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
WHO-ATC N05CF01
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
Code System Code Type Description
ECHA (EC/EINECS)
256-138-9
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
DRUG BANK
DB01198
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
CAS
43200-80-2
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
MERCK INDEX
M11663
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY Merck Index
PUBCHEM
5735
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY SWITZERF
EPA CompTox
43200-80-2
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
MESH
C515050
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
EVMPD
SUB00188MIG
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
IUPHAR
7430
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
INN
4462
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
NCI_THESAURUS
C80279
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
RXCUI
40001
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY RxNorm
WIKIPEDIA
ZOPICLONE
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY
ChEMBL
CHEMBL135400
Created by admin on Tue Mar 06 10:54:31 UTC 2018 , Edited by admin on Tue Mar 06 10:54:31 UTC 2018
PRIMARY