Page last updated: 2024-11-04

zopiclone

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Description

zopiclone: S(+)-enantiomer of racemic zopiclone; azabicyclo(4.3.0)nonane; a nonbenzodiazepine; one of the so-called of Z drugs (zopiclone, eszopiclone, zolpidem, and zaleplon) for which there is some correlation with tumors; was term of zopiclone 2004-2007 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

zopiclone : A pyrrolo[3,4-b]pyrazine compound having a 4-methylpiperazine-1-carboxyl group at the 5-position, a 5-chloropyridin-2-yl group at the 6-position and an oxo-substituent at the 7-position. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

2,3-hexanediol: an aggregation pheromone of cerambycid beetles [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5735
CHEMBL ID135400
CHEBI ID32315
SCHEMBL ID44419
MeSH IDM0075579
PubMed CID519963
SCHEMBL ID24401
MeSH IDM0075579

Synonyms (117)

Synonym
HMS3267I08
BRD-A34309505-001-08-5
1-piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5h-pyrrolo[3,4-b]pyrazin-5-yl ester
zopiclone
imovane
zimovane
amoban
ximovan
rp-27267
BIOMOL-NT_000284
MLS000083579 ,
EU-0101270
BPBIO1_001146
LOPAC0_001270
einecs 256-138-9
zopiclone [ban:inn:jan]
zopiclonum [inn-latin]
zopiclona [inn-spanish]
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
amovane
brn 0768704
1-piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5h-pyrrolo(3,4-b)pyrazin-5-yl ester
rp 27267
DB01198
(+/-)-zopiclone
6-(5-chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]pyrazin-5-yl 4-methyl-1-piperazinecarboxylate
(+-)-zopiclone
43200-80-2
amoban (tn)
6-(5-chloropyrid-2-yl)-5-(4-methylpiperazin-1-yl)carbonyloxy-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]pyrazine
D01372
zopiclone (tn)
zopiclone (jan/inn)
NCGC00024993-04
NCGC00024993-03
smr000048685
MLS000028547
MLS001304058
MLS001201837
6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
Z 4900 ,
nsc-758463
CHEMBL135400
zopiclonum
zopiclona
CHEBI:32315 ,
[6-(5-chloropyridin-2-yl)-5-oxo-7h-pyrrolo[3,4-b]pyrazin-7-yl] 4-methylpiperazine-1-carboxylate
BBL010797
nsc758463
pharmakon1600-01503425
BCP9000663
CCG-205343
STK599439
NCGC00016108-05
NCGC00016108-06
NCGC00016108-04
AKOS005520380
zopiclone [inn:ban:jan]
nsc 758463
dea no. 2784
03a5orl08q ,
unii-03a5orl08q
27267 r.p.
compound 3 [pmid: 8863805]
gtpl7430
zopiclone [jan]
zopiclone [ep impurity]
4-methyl-1-piperazinecarboxylic acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5h-pyrrolo(3,4-b)pyrazin-5-yl ester
zopiclone [inn]
zopiclone [mi]
zopiclone [mart.]
6-(5-chloropyrid-2-yl)-5-(4-methylpiperazin-1-yl)carbonyloxy-7-oxo-6,7-dihydro-5h-pyrrolo(3,4-b)pyrazine
zopiclone [ep monograph]
zopiclone [who-dd]
HY-B0741
SCHEMBL44419
4-methyl-1-piperazinecarboxylic acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5h-pyrrolo[3,4-b] pyrazin-5-yl ester
s-zopiclone
W-106239
4-methyl-piperazine-1-carboxylic acid 6-(5-chloro-pyridin-2-yl)-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]pyrazin-5-yl ester
zopiclone, british pharmacopoeia (bp) reference standard
OPERA_ID_1759
DTXSID4041155
SR-01000000090-2
sr-01000000090
(rs)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]pyrazine-5-yl 4-methylpiperazine-1-carboxylate
zopiclone, european pharmacopoeia (ep) reference standard
zopiclone 1.0 mg/ml in acetonitrile
SR-01000000090-4
SR-01000000090-6
SR-01000000090-7
SBI-0051236.P002
HMS3713H22
bdbm50248251
zimovane ls
zileze 3.75
zileze 7.5
6-(5-chloropyridin-2-yl)-7-oxo-5h,6h,7h-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
VS-02685
Q220426
1169825-88-0
BCP28513
BRD-A34309505-001-10-1
HMS3746I05
zopiclone (1.0 mg/ml in acetonitrile)
1ST10124
zopiclone, 1mg/ml in acetonitrile
(ss)- or (rr)-2,3-hexanediol
2,3-hexanediol
hexane-2,3-diol
617-30-1
SCHEMBL24401
2,3-hexanediol #
rs-2,3-hexanediol
QCIYAEYRVFUFAP-UHFFFAOYSA-N
70859-22-2
DTXSID30334204

Research Excerpts

Overview

Zopiclone is a cyclopyrrolone with sedative-hypnotic effect used as hypnotic. It is a hypnosedative structurally unrelated to the benzodiazepines but operating at the same receptor complex.

ExcerptReferenceRelevance
"Zopiclone is a widely used hypnotic drug which is frequently detected in apprehended drivers. "( Driving under the influence of zopiclone: Elimination between two consecutive blood samples.
Bleka, Ø; Høiseth, G; Kristoffersen, L; Strand, MC, 2023
)
2.64
"Eszopiclone is a zopiclone dextrorotation, which is classified as a cyclopyrrolone."( Case report of acute liver injury caused by the eszopiclone in a patient with chronic liver disease.
Li, Z; Wu, T; Xin, G; Yu, G, 2021
)
1.43
"Zopiclone is a poorly soluble psychotherapeutic agent. "( The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion.
Aucamp, M; Liebenberg, W; Milne, M, 2015
)
2.15
"Zopiclone (ZO) is a chiral drug that undergoes extensive metabolism to N-desmethylzopiclone (N-Des-ZO) and zopiclone-N-oxide (N-Ox-ZO). "( A new and fast DLLME-CE method for the enantioselective analysis of zopiclone and its active metabolite after fungal biotransformation.
de Albuquerque, NC; de Gaitani, CM; de Oliveira, AR, 2015
)
2.1
"Zopiclone is a nonbenzodiazapine hypnotic used for the treatment of insomnia. "( Identification and quantitation of zopiclone in biological matrices using gas chromatography-mass spectrometry (GC-MS).
Harryman, LA; Norton, MC; Rohrig, TP, 2010
)
2.08
"Zopiclone is a common drug in forensic cases and it is frequently analyzed in biological materials using different analytical methods. "( Stability tests of zopiclone in whole blood.
Ahlner, J; Kronstrand, R; Kugelberg, FC; Nilsson, GH, 2010
)
2.13
"Zopiclone is a short-acting hypnotic drug used for treatment of insomnia and its stability has been described in some detail. "( Influence of pre-analytical conditions on the interpretation of zopiclone concentrations in whole blood.
Ahlner, J; Kronstrand, R; Kugelberg, FC; Nilsson, GH, 2011
)
2.05
"Zopiclone is a cyclopyrrolone with sedative-hypnotic effect used as hypnotic and acts like benzodiazepines."( Effects of Alprazolam, Zolpidem and Zopiclone, and of chronic inflammation on peripheral experimental algesia in Wistar rats.
Antonescu, A; Bogdan, M; Dobjanschi, L; Moş, I; Mureşan, M; Muţiu, G; Zdrîncă, M, 2011
)
1.37
"Zopiclone is a hypnosedative structurally unrelated to the benzodiazepines but operating at the same receptor complex. "( Comparison of the fatal toxicity index of zopiclone with benzodiazepines.
Fountain, J; McDowell, R; Reith, DM; Tilyard, M, 2003
)
2.03
"Eszopiclone is a new, single-isomer, non-benzodiazepine, cyclopyrrolone agent under investigation for the treatment of insomnia. "( Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia.
Amato, DA; Caron, J; McNabb, LJ; Roth, T; Zammit, GK, 2004
)
1.35
"Eszopiclone is a new hypnotic that has fewer side effects."( What's new in clinical pharmacology and therapeutics.
Chawla, PS; Kochar, MS, 2006
)
0.89
"Zopiclone is a short acting hypnotic, which is metabolised by cytochrome P450 (CYP) 3A4 and 2C8 in vitro. "( The CYP2C8 inhibitor gemfibrozil does not increase the plasma concentrations of zopiclone.
Backman, JT; Neuvonen, PJ; Tornio, A, 2006
)
2
"Zopiclone (RP 27 267) is an hypnotic with a chemical structure different from that of the benzodiazepines (BZD) or barbiturates. "( Pharmacological studies on zopiclone.
Bardone, MC; Blanchard, JC; Garret, C; Julou, L; Stutzmann, JM, 1983
)
2.01
"Zopiclone (RP 27 267) is an hypnotic with a chemical structure different from that of the benzodiazepines (BZD) or barbiturates. "( Pharmacological studies on zopiclone.
Bardone, MC; Blanchard, JC; Garret, C; Julou, L; Stutzmann, JM, 1982
)
2
"Zopiclone is a new nonbenzodiazepine hypnotic, the recommended dose of which is 7.5 mg. "( Effects of zopiclone as compared to flurazepam on sleep in women over 40 years of age.
Buytaert, G; Hoffman, G; Quadens, OP, 1983
)
2.1
"Zopiclone is a cyclopyrrolone derivative which exerts, in animal and man, an hypnotic activity comparable to that of flurazepam. "( Efficacy and tolerance of zopiclone in insomniac geriatric patients.
Deschenes, JP; Elie, R, 1983
)
2.01
"Zopiclone is a useful drug for the treatment of sleep disturbances, not only because of its efficacy, but also because of its tolerability."( Comparative study of zopiclone and pentobarbitone as hypnotics.
Mello de Paula, AJ, 1983
)
1.31
"Zopiclone is a new sedative showing a rapid onset of hypnotic effect and a relatively short duration of action. "( Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers.
Caille, G; du Souich, P; Lacasse, Y; Spenard, J; Vezina, M,
)
1.84
"Zopiclone is a useful drug for the treatment of sleep disturbances, not only because of its efficacy, but also because of its tolerability."( Comparative study of zopiclone and pentobarbitone as hypnotics.
Mello de Paula, AJ, 1982
)
1.3
"Zopiclone is a new nonbenzodiazepine hypnotic, the recommended dose of which is 7.5 mg. "( Effects of zopiclone as compared to flurazepam on sleep in women over 40 years of age.
Buytaert, G; Hoffman, G; Quadens, OP, 1982
)
2.1
"Zopiclone is a cyclopyrrolone derivative which exerts, in animal and man, an hypnotic activity comparable to that of flurazepam. "( Efficacy and tolerance of zopiclone in insomniac geriatric patients.
Deschenes, JP; Elie, R, 1982
)
2.01
"Zopiclone is a cyclopyrrolone derivative which possesses hypnotic activity. "( [Study of zopiclone with quantitative EEG analysis and topography].
Kato, M; Okuma, T; Tsukahara, Y; Yamadera, H, 1995
)
2.14
"Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABAA receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. "( Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic.
McTavish, D; Wadworth, AN,
)
3.02
"Zopiclone is a cyclopyrrolone hypnotic agent. "( Clinical pharmacokinetics of zopiclone.
Farinotti, R; Fernandez, C; Gimenez, F; Martin, C, 1995
)
2.03
"Zopiclone is a new short half-life cyclopyrrolone hypnotic agent acting at the GABA-benzodiazepine receptor complex. "( Acute, subchronic and discontinuation effects of zopiclone on sleep EEG and nocturnal melatonin secretion.
Bauer, H; Benkert, O; Hiemke, C; Mann, K; Röschke, J; Wetzel, H, 1996
)
1.99
"Zopiclone is a non-benzodiazepine hypnotic which was first reviewed in Drugs in 1986. "( Zopiclone. An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia.
Lamb, HM; Langtry, HD; Noble, S, 1998
)
3.19
"Zopiclone is a widely prescribed, nonbenzodiazepine hypnotic that is extensively metabolized by the liver in humans. "( Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism.
Beaune, P; Becquemont, L; Escaffre, O; Funck-Brentano, C; Jaillon, P; Mouajjah, S, 1999
)
2.01
"Zopiclone is a cyclopyrrolone hypnosedative that is chemically unrelated to the benzodiazepines but nevertheless potentiates gamma-aminobutyric acid-mediated neuronal inhibition, and has demonstrated proven efficacy and good tolerability in the treatment of insomnia over 15 years of use. "( A comparative assessment of the risks and benefits of zopiclone: a review of 15 years' clinical experience.
Hajak, G, 1999
)
1.99
"Zopiclone (Zimovane) is a cyclopyrrolone compound which exhibits hypnotic and sedative effects while also exhibiting anticonvulsant and muscle relaxant activities. "( A method for the rapid detection of the zopiclone degradation product 2-amino-5-chloropyridine.
Forrest, AR; Galloway, JH; Marsh, ID; Newton, CM,
)
1.84
"Zopiclone is a cyclopyrrolone that is used clinically as a hypnotic. "( Characterization of the interaction of zopiclone with gamma-aminobutyric acid type A receptors.
Davies, M; Derry, JM; Dunn, SM; Martin, IL; Newell, JG, 2000
)
2.02
"Zopiclone is a hypnosedative with clinical effects similar to benzodiazepines but thought to have less potential for rebound insomnia and withdrawal effects. "( Validation of a high-performance liquid chromatographic method for the enantiospecific quantitation of zopiclone in plasma.
Alderman, CP; Gebauer, MG, 2002
)
1.97
"Zopiclone is a benzodiazepine-like hypnotic that was believed not to have any abuse potential. "( Chromatographic screening for zopiclone and metabolites in urine using liquid chromatography and liquid chromatography-mass spectrometry techniques.
Beck, O; Bodin, K; Nordgren, HK, 2002
)
2.05
"Zopiclone is a new hypnotic belonging to the cyclopyrrolone chemical class."( Zopiclone, the third generation hypnotic: a clinical overview.
Maillard, F; Musch, B, 1990
)
2.44
"Zopiclone is an effective hypnotic comparable to temazepam."( A double-blind placebo-controlled trial of zopiclone 7.5 mg and temazepam 20 mg in insomnia.
Hassan, R; Ngen, CC, 1990
)
1.26
"Zopiclone is a new hypnotic cyclopyrrolone with a short elimination half-life (5.3 h). "( Steady state pharmacokinetics of zopiclone during multiple oral dosing (7.5 mg nocte) in patients with severe chronic renal failure.
De Meyer, M; Frydman, A; Gaillot, J; Le Liboux, A; Maillard, F; Mignon, F; Viron, B, 1990
)
2
"Zopiclone is a new cyclopyrrolone derivative which exerts pharmacological activities similar to those of benzodiazepines in behavioral and biochemical studies. "( Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat.
Kumasaka, Y; Ueki, S; Yamamoto, T, 1989
)
2.03
"Zopiclone would appear to be a useful hypnotic for those involved in skilled work."( Efficacy of zopiclone in middle age.
Nicholson, AN; Stone, BM, 1987
)
1.37
"Zopiclone is a non-benzodiazepine hypnotic with a pharmacological spectrum of activity which resembles that of the benzodiazepines (BZD), but it binds to the GABA complex at a site different from the BZD receptor. "( Zopiclone, a cyclopyrrolone hypnotic: review of properties.
Brun, JP, 1988
)
3.16

Effects

Zopiclone has a relatively low propensity to cause residual clinical effects. It has a chiral centre, and demonstrates stereoselective pharmacokinetics.

Zopiclone has been proven as a drug that favourably balances sleep induction and maintenance as well as an improvement in daytime well-being. The drug has a relatively low propensity to cause residual clinical effects (such as difficulty in waking or reduced morning concentration)

ExcerptReferenceRelevance
"Zopiclone has a relatively low propensity to cause residual clinical effects (such as difficulty in waking or reduced morning concentration)."( Zopiclone. An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia.
Lamb, HM; Langtry, HD; Noble, S, 1998
)
2.46
"Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics."( Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem.
Chouinard, G; Lefko-Singh, K; Teboul, E, 1999
)
1.02
"Zopiclone has the potential for being an agent of abuse and addiction. "( Zopiclone: is it a pharmacologic agent for abuse?
Cimolai, N, 2007
)
3.23
"Zopiclone has a relatively low propensity to cause residual clinical effects (such as difficulty in waking or reduced morning concentration)."( Zopiclone. An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia.
Lamb, HM; Langtry, HD; Noble, S, 1998
)
2.46
"Zopiclone has been proven as a drug that favourably balances sleep induction and maintenance as well as an improvement in daytime well-being (efficacy) with a low potential for adverse effects (safety) in the symptomatic treatment of insomnia."( Clinical management of patients with insomnia. The role of zopiclone.
Hajak, G; Rodenbeck, A, 1996
)
1.26
"Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics."( Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem.
Chouinard, G; Lefko-Singh, K; Teboul, E, 1999
)
1.02
"Zopiclone dependence has repeatedly been reported in patients with pre-existing substance-related addictions, and in patients with other psychiatric disorders. "( [A case of primary zopiclone dependence].
Brüne, M; Kahlert, I, 2001
)
2.08

Actions

ExcerptReferenceRelevance
"Zopiclone induced an increase in respiratory frequency."( Effect of zopiclone and diazepam on ventilatory response in normal human subjects.
Nielsen, SP; Ranløv, PJ, 1987
)
1.4

Treatment

Zopiclone-treated patients reported themselves to be less impaired by daytime sedation than patients treated with the medium- and long-acting hypnosedatives flurazepam, nitrazepam and flunitrazepAm. Zopiclones produced significantly more taste disturbance and drowsiness.

ExcerptReferenceRelevance
"Zopiclone-treated patients reported themselves to be less impaired by daytime sedation than patients treated with the medium- and long-acting hypnosedatives flurazepam, nitrazepam and flunitrazepam."( A comparative assessment of the risks and benefits of zopiclone: a review of 15 years' clinical experience.
Hajak, G, 1999
)
1.27
"Zopiclone treatment produced significantly more taste disturbance and drowsiness."( Zopiclone in insomniac shiftworkers. Evaluation of its hypnotic properties and its effects on mood and work performance.
Billings, BJ; Bourgouin, J; Monchesky, TC; Phillips, R, 1989
)
2.44

Toxicity

The most common adverse event related to eszopiclone was unpleasant taste. There is a lack of documentation on the adverse effects of zopiclones.

ExcerptReferenceRelevance
" These benzodiazepines are not free of daytime adverse effects, particularly drowsiness, dependency potential, rebound insomnia and habituation to the drug effect."( Prescribing short-acting hypnosedatives. Current recommendations from a safety perspective.
Wheatley, D,
)
0.13
" This review of relevant literature has revealed a lack of documentation on the adverse effects of zopiclone."( [Adverse effects of zopiclone].
Bramness, JG; Olsen, H, 1998
)
0.84
"Tianeptine appears to be as effective and as safe as paroxetine for the ambulatory treatment of major depression."( Efficacy and safety of tianeptine in major depression: evidence from a 3-month controlled clinical trial versus paroxetine.
Azoulay, P; Septien, L; Waintraub, L, 2002
)
0.31
" Treatment was well tolerated by patients, and the most common treatment-related adverse event was unpleasant taste."( An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults.
Amato, D; Caron, J; Rosenberg, R; Roth, T, 2005
)
0.59
" Treatment was well tolerated; the most common adverse event related to eszopiclone was unpleasant taste."( Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia.
Amato, DA; Caron, J; McNabb, LJ; Roth, T; Zammit, GK, 2004
)
0.86
" The most frequent treatment-related adverse event was unpleasant taste."( A 2-week efficacy and safety study of eszopiclone in elderly patients with primary insomnia.
Amato, D; Erman, M; McCall, WV; Rosenberg, R; Scharf, M; Seiden, D; Wessel, TC, 2005
)
0.6
" While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia."( Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study.
Aldus, C; Arthur, A; Ballard, C; Boyd, PJ; Fox, C; Howard, R; Loke, YK; Maidment, I; Richardson, K; Savva, GM; Steel, N, 2020
)
0.56
" We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines."( Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study.
Aldus, C; Arthur, A; Ballard, C; Boyd, PJ; Fox, C; Howard, R; Loke, YK; Maidment, I; Richardson, K; Savva, GM; Steel, N, 2020
)
0.56

Pharmacokinetics

Zopiclone is a new hypnotic cyclopyrrolone with a short elimination half-life (5.5 hours) Repeated once daily dosing did not markedly alter the peak plasma zopicl one concentration or the pharmacokinetic parameters of absorption or elimination. The absorption of zopicLone was rapid, the observed plasma peak concentration and 95 per cent of all absorption occurred within one hour.

ExcerptReferenceRelevance
"Zopiclone is a new hypnotic cyclopyrrolone with a short elimination half-life (5."( Steady state pharmacokinetics of zopiclone during multiple oral dosing (7.5 mg nocte) in patients with severe chronic renal failure.
De Meyer, M; Frydman, A; Gaillot, J; Le Liboux, A; Maillard, F; Mignon, F; Viron, B, 1990
)
2
" The carrier of hypnotic activity is the parent compound; however, knowledge of its metabolic profile is essential for the understanding of pharmacokinetic changes in various pathophysiological conditions."( Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency.
Dreyfus, JF; Gaillot, J; Houghton, GW; Le Roux, Y, 1987
)
0.54
" Repeated once daily dosing did not markedly alter the peak plasma zopiclone concentration or the pharmacokinetic parameters of absorption or elimination."( A repeated dose pharmacokinetic study of a new hypnotic agent, zopiclone (Imovane).
Dennis, MJ; Houghton, GW; Martin, BK; Templeton, R, 1985
)
0.75
" Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min)."( Pharmacokinetics and metabolism of zopiclone.
Dreyfus, JF; Gaillot, J; Heusse, D; Hougton, GW; Marc Aurele, J, 1983
)
0.54
" The absorption of zopiclone was rapid, the observed plasma peak concentration and 95 per cent of all absorption occurring within one hour."( Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers.
Caille, G; du Souich, P; Lacasse, Y; Spenard, J; Vezina, M,
)
0.72
" Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min)."( Pharmacokinetics and metabolism of zopiclone.
Dreyfus, JF; Gaillot, J; Heusse, D; Hougton, GW; Marc Aurele, J, 1982
)
0.54
"001), Cmax values of 87."( Pharmacokinetics of zopiclone and its enantiomers in Caucasian young healthy volunteers.
Farinotti, R; Fernandez, C; Gimenez, F; Maradeix, V; Thuillier, A,
)
0.45
"Itraconazole significantly increased the Cmax of zopiclone from 49 to 63 ng."( Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone.
Jalava, KM; Neuvonen, PJ; Olkkola, KT, 1996
)
0.78
"Itraconazole has a statistically significant pharmacokinetic interaction with zopiclone but this is only of limited clinical importance, at least in young adults."( Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone.
Jalava, KM; Neuvonen, PJ; Olkkola, KT, 1996
)
0.76
" The duration of action of zaleplon, zolpidem and zopiclone can be related to their individual pharmacokinetic profile, which subsequently determines the time course of drug effect."( Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone.
Drover, DR, 2004
)
0.79
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35

Compound-Compound Interactions

ExcerptReferenceRelevance
" These effects were examined independently and in combination with ethanol effects."( Effects of flurazepam and zopiclone on the performance of chronic insomniac patients: a study of ethanol-drug interaction.
Buck, L; Csima, A; Mamelak, M; Price, V; Smiley, A, 1987
)
0.57
" The present comparative study was performed to examine the effects of the oral administration of Ro 41-3696, nitrazepam or zopiclone alone and in combination with a 'social' dose of ethanol on mouse hippocampal EEG."( Changes in mouse hippocampal EEG characteristics after oral administration of Ro 41-3696, nitrazepam, or zopiclone alone and in combination with ethanol.
Himori, N; Tanaka, Y; Tsuboi, M, 1994
)
0.71
" Rifampicin significantly induced the metabolism of the newer hypnosedatives and decreased their sedative effects, indicating that a dose increase of these agents may be necessary when they are administered with rifampicin."( Clinically important drug interactions with zopiclone, zolpidem and zaleplon.
Greenblatt, DJ; Hesse, LM; von Moltke, LL, 2003
)
0.58

Bioavailability

Zopiclone is rapidly absorbed, with a bioavailability of approximately 80%. Trimipramine decreased the relative bioavailability determined for zopicl one by 13%. The relative bio availability of oral racemic zopicLone is about 80%.

ExcerptReferenceRelevance
" In 18 patients with renal insufficiency, the only major modification was an increased bioavailability (F of 115%) probably due to a relative decrease of the Vdc."( Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency.
Dreyfus, JF; Gaillot, J; Houghton, GW; Le Roux, Y, 1987
)
0.54
" ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded."( Pharmacokinetics and metabolism of zopiclone.
Dreyfus, JF; Gaillot, J; Heusse, D; Hougton, GW; Marc Aurele, J, 1983
)
0.54
" Trimipramine decreased the relative bioavailability determined for zopiclone by 13."( Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers.
Caille, G; du Souich, P; Lacasse, Y; Spenard, J; Vezina, M,
)
0.63
" ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded."( Pharmacokinetics and metabolism of zopiclone.
Dreyfus, JF; Gaillot, J; Heusse, D; Hougton, GW; Marc Aurele, J, 1982
)
0.54
" After oral administration, zopiclone is rapidly absorbed, with a bioavailability of approximately 80%."( Clinical pharmacokinetics of zopiclone.
Farinotti, R; Fernandez, C; Gimenez, F; Martin, C, 1995
)
0.88
" Although zaleplon has a much lower bioavailability (30%), the treatment dose is similar to zolpidem and zopiclone (bioavilaibility of 70%) because of the increased potency of zaleplon."( Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone.
Drover, DR, 2004
)
0.75
" The relative bioavailability of oral racemic zopiclone is about 80%."( Eszopiclone.
Halas, CJ, 2006
)
1.31
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010
)
0.36

Dosage Studied

The purpose of the study was to ascertain whether the new hypnotic, zopiclone, was likely to produce rebound problems after short-term use.

ExcerptRelevanceReference
" For zolpidem, receptor binding was reduced in cortex without a dose-response effect and no effect was observed on cerebellar binding."( Benzodiazepine receptor binding of nonbenzodiazepines in vivo: alpidem, zolpidem and zopiclone.
Byrnes, JJ; Greenblatt, DJ; Miller, LG, 1992
)
0.51
"Sixty insomniac patients participated in a controlled double-blind parallel group study designed to investigate the dose-response relationship of zopiclone."( A dose-range finding study of zopiclone in insomniac patients.
Dimitri, R; Le Morvan, P; Nair, NP; Schwartz, G; Thavundayil, JX, 1990
)
0.77
" The pharmacokinetic values obtained were compared with the corresponding values found in healthy young volunteers given the same repeated dosage regimen."( Steady state pharmacokinetics of zopiclone during multiple oral dosing (7.5 mg nocte) in patients with severe chronic renal failure.
De Meyer, M; Frydman, A; Gaillot, J; Le Liboux, A; Maillard, F; Mignon, F; Viron, B, 1990
)
0.56
"The purpose of the study was to ascertain whether the new hypnotic, zopiclone, was likely to produce rebound problems after short-term use, in comparison with placebo and a standard hypnotic, temazepam, and whether tapering the dosage lessened any such effects."( Subjective effects during administration and on discontinuation of zopiclone and temazepam in normal subjects.
Frcka, G; Lader, M, 1987
)
0.74
"Eleven volunteers were dosed once daily for 14 days with zopiclone (7."( A repeated dose pharmacokinetic study of a new hypnotic agent, zopiclone (Imovane).
Dennis, MJ; Houghton, GW; Martin, BK; Templeton, R, 1985
)
0.75
" Diazepam shifted GABA dose-response curves to the left by decreasing the apparent KD but without altering the apparent Vmax (Lineweaver-Burk analysis)."( Benzodiazepine receptor ligand actions on GABA responses. Benzodiazepines, CL 218872, zopiclone.
Macdonald, RL; Skerritt, JH, 1984
)
0.49
" The maximal dosage was 8 capsules per day (2."( Studies on the dependence-inducing potential of zopiclone and triazolam.
Boissl, K; Delmotte, M; Dreyfus, JF, 1983
)
0.52
" The maximal dosage was 8 capsules per day (2."( Studies on the dependence-inducing potential of zopiclone and triazolam.
Boissl, K; Delmotte, M; Dreyfus, JF, 1982
)
0.52
" The results indicate that zopiclone is an active hypnotic compound, comparable in its effects to those of nitrazepam, the higher dosage being best adapted to the type of patients included in the study."( Comparison of nitrazepam and zopiclone in psychiatric patients.
Brun, JP; Dreyfus, JF; Pull, CB, 1983
)
0.85
" The results indicate that zopiclone is an active hypnotic compound, comparable in its effects to those of nitrazepam, the higher dosage being best adapted to the type of patients included in the study."( Comparison of nitrazepam and zopiclone in psychiatric patients.
Brun, JP; Dreyfus, JF; Pull, CB, 1982
)
0.85
" Secondary criteria confirmed the antidepressant efficacy of both medications, with no difference between tianeptine and paroxetine (Hamilton Depression Rating Scale global score at endpoint, Clinical Global Impression final scores, number of responders, delay-to-response, rate of dosage doubling at day 21)."( Efficacy and safety of tianeptine in major depression: evidence from a 3-month controlled clinical trial versus paroxetine.
Azoulay, P; Septien, L; Waintraub, L, 2002
)
0.31
" At a clinically prescribed dosage these sleep inducers have no remarkable effect on cognitive or attentional functions but increase sleepiness of the subjects."( Effects of zolpidem and zopiclone on cognitive and attentional function in young healthy volunteers: an event-related potential study.
Hayashida, S; Kanno, O; Nakagome, K; Nakajima, T; Sasaki, T; Takazawa, S, 2000
)
0.61
" The recommended dosing to improve sleep onset and/or maintenance is 2mg or 3mg for adult patients (aged 18-64 years) and 2mg for older adult patients (aged > or =65 years)."( Eszopiclone: esopiclone, estorra, S-zopiclone, zopiclone--Sepracor.
, 2005
)
1.05
" Dosing should be individualized, and the lowest effective dose should be used to minimize the risk of adverse events."( Eszopiclone.
Halas, CJ, 2006
)
1.06
" Ideally, prescriptions should be given for a short period of time and within the recommended dosage guidelines."( Zopiclone: is it a pharmacologic agent for abuse?
Cimolai, N, 2007
)
1.78
"To assess the effects of post-bedtime dosing with indiplon on next-day function in adults and the elderly."( Post-bedtime dosing with indiplon in adults and the elderly: results from two placebo-controlled, active comparator crossover studies in healthy volunteers.
Burke, PJ; Farber, RH, 2008
)
0.35
"Adsorptive stripping voltammetric (AdSV) techniques were proposed for the direct quantitative determination of zopiclone (ZP) in spiked human urine and tablet dosage forms for first time."( Adsorptive stripping voltammetric determination of zopiclone in tablet dosage forms and human urine.
Yilmaz, S, 2009
)
0.82
"This pilot study suggests that a higher dosage of zolpidem (> 10 mg/d) is the key risk predictor for CSBs."( Risk predictors for hypnosedative-related complex sleep behaviors: a retrospective, cross-sectional pilot study.
Chen, HC; Hwang, TJ; Liao, SC; Lin, YT; Ni, HC, 2010
)
0.36
" This study investigated zopiclone stability differences between spiked and authentic whole blood from subjects dosed with zopiclone."( Influence of pre-analytical conditions on the interpretation of zopiclone concentrations in whole blood.
Ahlner, J; Kronstrand, R; Kugelberg, FC; Nilsson, GH, 2011
)
0.91
"5 mg), and placebo on driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects following bedtime dosing and a middle of the night awakening."( Next-day effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on highway driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects.
de Senerpont Domis, LM; de Vries, JM; Mets, MA; Olivier, B; Verster, JC; Volkerts, ER, 2011
)
0.64
" Nighttime dosing of both eszopiclone (3 mg) and racemic zopiclone (7."( A method to assess the dissipation of the [corrected] residual effects of [corrected] hypnotics: eszopiclone versus zopiclone.
Atzori, G; Boyle, J; Cooper, JA; Dijk, DJ; Gandhi, P; Groeger, JA; Jones, S; Paska, W; Rockett, C; Scott, J, 2012
)
0.89
" We did not find a dose-response effect."( Pharmacological interventions for sleepiness and sleep disturbances caused by shift work.
Costa, G; Driscoll, TR; Isotalo, LK; Liira, J; Ruotsalainen, JH; Sallinen, M; Verbeek, JH, 2014
)
0.4
"The objective of this study was to determine the next-day residual effects of acute and steady-state nighttime dosing of flibanserin on simulated driving performance and cognitive function in healthy premenopausal women."( Next-day residual effects of flibanserin on simulated driving performance in premenopausal women.
Hochadel, T; Kay, GG; Kim, NN; Natarajan, KK; Sicard, E, 2017
)
0.46
" Simulated driving assessments were conducted 9 hr after dosing and cognitive function tests were administered immediately before or during the driving assessment."( Next-day residual effects of flibanserin on simulated driving performance in premenopausal women.
Hochadel, T; Kay, GG; Kim, NN; Natarajan, KK; Sicard, E, 2017
)
0.46
"The present study involved segmental testing of hair in two clinical cases with known dosage histories."( Segmental Hair Analysis-Interpretation of the Time of Drug Intake in Two Patients Undergoing Drug Treatment.
Johansen, SS; Linnet, K; Nielsen, MKK; Wang, X, 2019
)
0.51
" No significant difference in concentrations was found between the two dosing groups for either zopiclone or N-desmethylzopiclone."( Distribution of zopiclone and main metabolites in hair following a single dose.
Hansen, SL; Johansen, SS; Kronstrand, R; Nielsen, MKK; Nilsson, G, 2020
)
1.12
" We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines."( Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study.
Aldus, C; Arthur, A; Ballard, C; Boyd, PJ; Fox, C; Howard, R; Loke, YK; Maidment, I; Richardson, K; Savva, GM; Steel, N, 2020
)
0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
central nervous system depressantA loosely defined group of drugs that tend to reduce the activity of the central nervous system.
sedativeA central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
pyrrolopyrazine
monochloropyridineA chloropyridine in which only one chlorine is attached to the pyridine ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (25)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, ATP-DEPENDENT DNA HELICASE Q1Homo sapiens (human)Potency1.41250.125919.1169125.8920AID2549
Microtubule-associated protein tauHomo sapiens (human)Potency0.89130.180013.557439.8107AID1460
67.9K proteinVaccinia virusPotency3.64260.00018.4406100.0000AID720579; AID720580
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency89.12510.035520.977089.1251AID504332
muscleblind-like protein 1 isoform 1Homo sapiens (human)Potency11.22020.00419.962528.1838AID2675
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
ATP-binding cassette sub-family C member 3Homo sapiens (human)IC50 (µMol)133.00000.63154.45319.3000AID1473740
Multidrug resistance-associated protein 4Homo sapiens (human)IC50 (µMol)133.00000.20005.677410.0000AID1473741
Bile salt export pumpHomo sapiens (human)IC50 (µMol)133.00000.11007.190310.0000AID1473738
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.505710.0000AID42333
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.497310.0000AID42333
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.498810.0000AID42333
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.504610.0000AID42333
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.506510.0000AID42333
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.505710.0000AID42333
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
GABA theta subunitRattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
Canalicular multispecific organic anion transporter 1Homo sapiens (human)IC50 (µMol)133.00002.41006.343310.0000AID1473739
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)IC50 (µMol)0.02900.00010.507510.0000AID42333
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (41)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
bile acid and bile salt transportATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transportATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
leukotriene transportATP-binding cassette sub-family C member 3Homo sapiens (human)
monoatomic anion transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transport across blood-brain barrierATP-binding cassette sub-family C member 3Homo sapiens (human)
prostaglandin secretionMultidrug resistance-associated protein 4Homo sapiens (human)
cilium assemblyMultidrug resistance-associated protein 4Homo sapiens (human)
platelet degranulationMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
bile acid and bile salt transportMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transportMultidrug resistance-associated protein 4Homo sapiens (human)
urate transportMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 4Homo sapiens (human)
leukotriene transportMultidrug resistance-associated protein 4Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 4Homo sapiens (human)
guanine nucleotide transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
negative regulation of gene expressionCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bile acid and bile salt transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
heme catabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic export from cellCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transepithelial transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
leukotriene transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
monoatomic anion transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (24)

Processvia Protein(s)Taxonomy
ATP bindingATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type xenobiotic transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type bile acid transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATP hydrolysis activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
icosanoid transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
guanine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
urate transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type bile acid transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
protein bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
organic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type xenobiotic transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP hydrolysis activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (17)

Processvia Protein(s)Taxonomy
plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basal plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basolateral plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
nucleolusMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi apparatusMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
platelet dense granule membraneMultidrug resistance-associated protein 4Homo sapiens (human)
external side of apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
cell surfaceCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
intercellular canaliculusCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (89)

Assay IDTitleYearJournalArticle
AID496825Antimicrobial activity against Leishmania mexicana2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID496820Antimicrobial activity against Trypanosoma brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID496828Antimicrobial activity against Leishmania donovani2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID497005Antimicrobial activity against Pneumocystis carinii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID496821Antimicrobial activity against Leishmania2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID496823Antimicrobial activity against Trichomonas vaginalis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1325013Drug metabolism assessed as decarboxylated metabolite formation2016Bioorganic & medicinal chemistry letters, 11-01, Volume: 26, Issue:21
Synthesis and pharmacological evaluation of functionalized isoindolinones on GABA-activated chloride currents in rat cerebellum granule cells in culture.
AID1325005Agonist activity at GABA alpha1beta2beta3gamma2 receptor Bzd binding site in Sprague-Dawley rat cerebellar granule cells assessed as increase in GABA-activated chloride currents at 1 uM by whole-cell patch clamp technique relative to control2016Bioorganic & medicinal chemistry letters, 11-01, Volume: 26, Issue:21
Synthesis and pharmacological evaluation of functionalized isoindolinones on GABA-activated chloride currents in rat cerebellum granule cells in culture.
AID1473739Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID496817Antimicrobial activity against Trypanosoma cruzi2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID42333Binding affinity against central benzodiazepine receptor(CBR).1996Journal of medicinal chemistry, Oct-11, Volume: 39, Issue:21
Molecular basis of peripheral vs central benzodiazepine receptor selectivity in a new class of peripheral benzodiazepine receptor ligands related to alpidem.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1473738Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID496831Antimicrobial activity against Cryptosporidium parvum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID496819Antimicrobial activity against Plasmodium falciparum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID539464Solubility of the compound in 0.1 M phosphate buffer at 600 uM at pH 7.4 after 24 hrs by LC/MS/MS analysis2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate.
AID496827Antimicrobial activity against Leishmania amazonensis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID496829Antimicrobial activity against Leishmania infantum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID496826Antimicrobial activity against Entamoeba histolytica2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473741Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID496824Antimicrobial activity against Toxoplasma gondii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID468443Inhibition of human FAAH at 1 uM2009Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23
Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.
AID496830Antimicrobial activity against Leishmania major2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1473740Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID496832Antimicrobial activity against Trypanosoma brucei rhodesiense2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID496818Antimicrobial activity against Trypanosoma brucei brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1224864HCS microscopy assay (F508del-CFTR)2016PloS one, , Volume: 11, Issue:10
Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (718)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990136 (18.94)18.7374
1990's164 (22.84)18.2507
2000's205 (28.55)29.6817
2010's174 (24.23)24.3611
2020's39 (5.43)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 112.03

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index112.03 (24.57)
Research Supply Index6.86 (2.92)
Research Growth Index4.58 (4.65)
Search Engine Demand Index207.82 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (112.03)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials204 (27.31%)5.53%
Trials0 (0.00%)5.53%
Reviews77 (10.31%)6.00%
Reviews0 (0.00%)6.00%
Case Studies68 (9.10%)4.05%
Case Studies0 (0.00%)4.05%
Observational5 (0.67%)0.25%
Observational0 (0.00%)0.25%
Other393 (52.61%)84.16%
Other8 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (33)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Double-blind, Randomized, Parallel Group Study to Determine the Effect of Initial Prescription of Zopiclone on the Level of Compliance With CPAP in Adult Patients Treated for OSA at 26 Weeks [NCT01369576]Phase 3264 participants (Actual)Interventional2011-05-31Completed
A Single-center, Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, 4-way Cross-over Study to Assess Next-day Driving Performance Following Single and Multiple Evening Administrations of ACT-541468 in Middle-aged and Elderly Subjects [NCT03892902]Phase 156 participants (Actual)Interventional2019-03-25Completed
Driving Simulator Performance Related to Serum Concentrations of the Benzodiazepine-like Hypnotic Zopiclone [NCT01257165]0 participants (Actual)Interventional2012-08-31Withdrawn
Effectiveness of Nonspecific Methods of Treatment and Zopiclone for Chronic Insomnia [NCT03339583]Phase 242 participants (Actual)Interventional2015-04-07Completed
SleepSure: A Randomised Controlled Trial to Assess the Effects of Eye Masks and Earplugs on Hospital Inpatient Sleep [NCT02732912]Phase 3206 participants (Actual)Interventional2016-11-25Completed
A Multiple Dose Study to Evaluate Next Day Effects of MK-4305 on Driving Performance in Healthy Non-Elderly Subjects [NCT01311882]Phase 128 participants (Actual)Interventional2011-04-30Completed
The Effect of Alcohol Hangover and Night-time Zopiclone on Next-morning Spatial Perception in Healthy Young Volunteers [NCT03632408]Phase 116 participants (Anticipated)Interventional2018-09-30Not yet recruiting
MELA Study - Hedonic Study on the Taste of Drugs Crushed in Food: Observational Study Involving 16 Healthy Volunteers [NCT02570581]Phase 116 participants (Actual)Interventional2014-06-30Completed
Pharmacological Treatment of Insomnia in Palliative Care: A Randomized, Double-blind, Placebo Controlled, Parallel-group, Multicenter Trial Investigating the Short Time Effect of Zopiclone on Self-reported Sleep Quality in Patients With Advanced Cancer Wh [NCT02807922]Phase 443 participants (Actual)Interventional2016-11-15Completed
Lemborexant vs Zopiclone vs Clonidine for Insomnia Treatment in Chronic Pain Patients [NCT05618002]150 participants (Anticipated)Observational2022-11-08Recruiting
A Randomized Double-blind, Placebo-controlled, 4-period Cross-over Study to Assess the Effect of Single and Multiple Doses of 1.5 mg and 4.5 mg Org 50081 and a Single Dose of 7.5 mg Zopiclone on Next-day Driving Ability and Psychomotor Performance in Heal [NCT00798395]Phase 132 participants (Actual)Interventional2007-10-31Completed
A Phase III, Non-inferiority, Double-blind, Unicenter Clinical Trial With Two Treatment Arms - Test Group With Eszopiclone 3 mg Versus Zopiclone 7.5 mg - for the Treatment of Insomnia [NCT01100164]Phase 3263 participants (Actual)Interventional2011-03-31Completed
A Study to Investigate the Next-day Residual Effects of TS-142 in Healthy Elderly Subjects [NCT05819710]Phase 143 participants (Actual)Interventional2023-05-15Completed
Clonidine is Better Than Zopiclone for Insomnia Treatment in Chronic Pain Patients [NCT05277038]150 participants (Actual)Observational [Patient Registry]2022-03-01Completed
The Effects of a Single Evening Dose of 3 mg Eszopiclone on Next Day Driving Ability and Psychomotor/Memory Function in Healthy Volunteers Compared to Placebo [NCT00368160]Phase 132 participants (Actual)Interventional2004-03-31Completed
[NCT00295386]Phase 40 participants Interventional2004-01-31Completed
A Randomised, Double-blind, Double-dummy, Placebo-controlled, 3-way Crossover Study to Evaluate Potential Next-day Residual Effects of a Single Evening Dose of 3mg Eszopiclone and 7.5mg Zopiclone in Healthy Adult Subjects. [NCT00699608]Phase 391 participants (Actual)Interventional2008-07-31Completed
Adaptative Servoventilation Compliance in Left Ventricular Dysfunction Patients With Central Sleep Apnea: Benefit of One Month Hypnotic (Zopiclone) Versus Placebo [NCT02820441]Phase 42 participants (Actual)Interventional2016-05-31Terminated
A Study of Changes in Blood Gases, Disturbance of Breath During Sleep and Cardiovascular Co-morbidity in Patients With COPD in Different Stages of the Disease, and the Effect of Alcohol, Supplementary Oxygen and Zopiclone on These Changes. [NCT00888342]150 participants (Actual)Interventional2009-05-31Completed
A Randomized, Double-Blind, Placebo- and Active-Controlled, 4-Period Crossover Study to Evaluate the Effect of Lemborexant Versus Placebo on Driving Performance in Healthy Adult and Elderly Subjects [NCT02583451]Phase 148 participants (Actual)Interventional2015-11-30Completed
Treatments for Insomnia in Patients With Parkinson's Disease: A Pilot Study [NCT01489982]Early Phase 120 participants (Actual)Interventional2011-01-31Completed
A Six-Month, Chronic Efficacy and Safety Study of Eszopiclone in Adult Subjects With Primary Insomnia: A Randomized Double-Blind, Placebo-Controlled Study [NCT00352144]Phase 3830 participants (Actual)Interventional2003-10-31Completed
Assessment of Two Modes of Premedication in Surgery - PREMED Study [NCT01549691]Phase 4455 participants (Anticipated)Interventional2012-03-31Completed
The Effect of Eszopiclone 3 mg Compared to Placebo on Daytime Function in Subjects With Insomnia Related to Rheumatoid Arthritis [NCT00367965]Phase 3153 participants (Actual)Interventional2004-02-29Completed
A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Ramelteon Compared to Placebo With Zopiclone as a Reference Arm in Adults With Chronic Insomnia [NCT00237497]Phase 3275 participants (Actual)Interventional2005-07-31Completed
A Study to Investigate the Residual Effects of Ramelteon (8 mg), Zopiclone (7.5 mg) and Placebo on Actual Driving, Memory, Psychomotor Performance and Mood [NCT00319215]Phase 130 participants Interventional2006-03-31Completed
The Efficacy of Eszopiclone 3 mg Compared to Placebo in the Treatment of Insomnia Secondary to Perimenopause or Menopause [NCT00366093]Phase 3410 participants (Actual)Interventional2004-02-29Completed
Assessment of Next-Morning Driving Performance After Middle of the Night Administration of Zolpidem Tartrate Sublingual Tablet 3.5 mg in Healthy Adult Volunteers: Single-center, Double-blind, Randomized, Placebo-controlled, Four-way Crossover Study [NCT01106859]Phase 140 participants (Actual)Interventional2010-06-30Completed
A Multicentric, Randomized, Double-Blind, Placebo- and Positive-Controlled 4-way Crossover Study to Evaluate the Effects of Single and Repeated Administration of Oral Seltorexant as an add-on Medication to an Antidepressant on On-Road Driving Performance [NCT04451187]Phase 163 participants (Actual)Interventional2020-07-16Completed
Effects of a Single Evening Dose of 3 mg Eszopiclone on Next Day Driving Ability and Psychomotor/Memory Function in Patients With Primary Insomnia Compared to Placebo [NCT00368056]Phase 332 participants (Actual)Interventional2005-04-30Completed
A Driving Performance Evaluation Study of TS-142 Using a Driving Simulator in Non-elderly and Elderly Healthy Subjects [NCT04696952]Phase 161 participants (Actual)Interventional2021-01-16Completed
Pharmacovigilance in Gerontopsychiatric Patients [NCT02374567]Phase 3407 participants (Actual)Interventional2015-01-31Terminated
Efficacy of Multimodal Analgesia Following Hip Arthroscopy [NCT03351439]100 participants (Actual)Interventional2018-04-06Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00699608 (15) [back to overview]Critical Flicker Fusion Test-Ascending Threshold
NCT00699608 (15) [back to overview]Coordination Score, as Assessed by the Linear Analogue Rating Scales
NCT00699608 (15) [back to overview]1-Back Percentage of Correct Responses
NCT00699608 (15) [back to overview]3-Back Reaction Time
NCT00699608 (15) [back to overview]3-Back Percentage of Correct Responses
NCT00699608 (15) [back to overview]Critical Flicker Fusion Test -Descending Threshold
NCT00699608 (15) [back to overview]1-Back Reaction Time
NCT00699608 (15) [back to overview]Mean Tracking Error Assessed During the Continuous Tracking Test (CTT)
NCT00699608 (15) [back to overview]Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test
NCT00699608 (15) [back to overview]Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test
NCT00699608 (15) [back to overview]Sedation Score, as Assessed by the Linear Analogue Rating Scales
NCT00699608 (15) [back to overview]Mood Score, as Assessed by the Linear Analogue Rating Scales
NCT00699608 (15) [back to overview]Mean Tracking Error (MTE) Assessed During the CTT
NCT00699608 (15) [back to overview]CTT Mean Reaction Time
NCT00699608 (15) [back to overview]Critical Flicker Fusion Test-Overall Threshold
NCT01106859 (9) [back to overview]Mean Standard Deviation of Speed (SDS) in the Highway Drive Test
NCT01106859 (9) [back to overview]Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold
NCT01106859 (9) [back to overview]Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold
NCT01106859 (9) [back to overview]Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy
NCT01106859 (9) [back to overview]Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy
NCT01106859 (9) [back to overview]Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy
NCT01106859 (9) [back to overview]Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs)
NCT01106859 (9) [back to overview]Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold
NCT01106859 (9) [back to overview]Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test
NCT02732912 (4) [back to overview]Use of Zopiclone (Night Sedation)
NCT02732912 (4) [back to overview]SleepSure (Questionnaire). A Short Questionnaire of the Quality and Quantity of Sleep, and Use of Aids.
NCT02732912 (4) [back to overview]Number of Falls
NCT02732912 (4) [back to overview]Length of Stay
NCT03339583 (17) [back to overview]Amount of Awakenings
NCT03339583 (17) [back to overview]N1 NREM Sleep Percentage
NCT03339583 (17) [back to overview]N2 NREM Sleep Percentage
NCT03339583 (17) [back to overview]N3 NREM Sleep Percentage
NCT03339583 (17) [back to overview]REM Sleep Percentage
NCT03339583 (17) [back to overview]Sleep Latency
NCT03339583 (17) [back to overview]Toronto Alexithymia Scale (TAS-20)
NCT03339583 (17) [back to overview]Insomnia Severity Index
NCT03339583 (17) [back to overview]Dysfunctional Beliefs About Sleep Scale
NCT03339583 (17) [back to overview]Beck Depression Inventory
NCT03339583 (17) [back to overview]Wake After Sleep Onset
NCT03339583 (17) [back to overview]Total Sleep Time
NCT03339583 (17) [back to overview]Sleep Efficiency
NCT03339583 (17) [back to overview]Trait Anxiety Subscale (STAI)
NCT03339583 (17) [back to overview]State Anxiety Subscale (STAI)
NCT03339583 (17) [back to overview]Sleep Hygiene Index
NCT03339583 (17) [back to overview]Pittsburgh Sleep Quality Index

Critical Flicker Fusion Test-Ascending Threshold

Critical Flicker Fusion (CFF) is a validated cognitive assessment task that provides an index of central nervous system (CNS) activity and attention modulated motion detection. Participants are required to discriminate flicker from fusion, and vice versa, in a set of four light-emitting diodes arranged in a one-centimetre square. These diodes are held in foveal fixation when viewed at a distance of one metre. Individual thresholds are determined on four ascending and four descending scales. The mean of the four ascending presentations give the ascending threshold frequency in hertz. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionhertz (Least Squares Mean)
7.5 hours post-dose, n=88, 87, 908 hours post-dose, n=89, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone30.8430.3029.9829.9029.9929.9129.9930.0630.28
Placebo30.6530.3130.2730.1030.1830.2030.2630.2030.31
Zopiclone30.9330.4130.1730.0030.0529.9730.1630.0430.56

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Coordination Score, as Assessed by the Linear Analogue Rating Scales

"Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Dizziness and Clumsiness scores are averaged to derive an overall Coordination score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired." (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionpoints on a scale (Least Squares Mean)
7.5 hours post-dose, n=89, 87, 908 hours post-dose, n=89, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 9011 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone50.3351.2149.5250.3849.4249.7250.6848.5147.45
Placebo49.0950.0349.2349.6849.0849.3748.6048.9748.20
Zopiclone52.4252.1051.7650.4151.4150.2750.4049.9649.82

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1-Back Percentage of Correct Responses

"The N-Back task requires the participant to indicate, using the mouse, whether the current stimulus presented on the screen and the one immediately before it visually match (i.e., one-back). In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 minutes. The percentage of correct responses is the percentage of correct responses given in 2 minutes." (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionpercentage of responses (Least Squares Mean)
7.5 hours post-dose, n=87, 87, 888 hours post-dose, n=89, 87, 898.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 86, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 86, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone92.292.092.891.691.292.292.092.694.0
Placebo93.993.393.693.592.993.094.493.093.4
Zopiclone90.489.589.689.490.792.091.791.992.0

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3-Back Reaction Time

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionmilliseconds (Least Squares Mean)
7.5 hours post-dose, n=87, 87, 888 hours post-dose, n=89, 87, 898.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 86, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 86, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone1020.91018.5997.71002.2992.1948.7961.5935.5903.2
Placebo959.5960.0925.9916.9932.9907.4900.3915.3876.2
Zopiclone1076.41042.21024.21007.8978.0987.5945.2940.4934.7

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3-Back Percentage of Correct Responses

"Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). In 3-back tasks, a comparison is made between the current stimulus and the two before the immediately preceding stimulus. In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 min. The percentage of correct responses is the percentage of correct responses given in 2 min." (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionpercentage of responses (Least Squares Mean)
7.5 hours post-dose, n=87, 87, 888 hours post-dose, n=89, 87, 898.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 86, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 86, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone80.482.381.178.980.282.081.383.283.6
Placebo84.683.582.483.382.183.482.681.782.9
Zopiclone76.976.878.377.376.979.279.779.881.1

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Critical Flicker Fusion Test -Descending Threshold

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four descending presentations from the CFF give the descending threshold frequency in hertz. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionhertz (Least Squares Mean)
7.5 hours post-dose, n=88, 87, 908 hours post-dose, n=89, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone28.3727.9527.7527.6427.8127.9627.9928.0328.69
Placebo29.0628.5228.4228.0728.1928.1828.4828.5328.57
Zopiclone28.0527.9527.5927.8927.7528.0628.1028.2028.48

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1-Back Reaction Time

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionmilliseconds (Least Squares Mean)
7.5 hours post-dose, n=87, 87, 888 hours post-dose, n=89, 87, 898.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 86, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 86, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone819.3783.7776.1784.5757.2760.8735.2716.9716.7
Placebo755.9752.7741.1734.8729.0724.7713.2718.5709.3
Zopiclone840.3805.8778.7791.1784.0759.5750.7741.7720.5

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Mean Tracking Error Assessed During the Continuous Tracking Test (CTT)

Analysis was performed on the mean of the five assessments conducted 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind) The CTT is a task (duration of 8 minutes) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the mean tracking error - the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind)

Interventionpixels (Least Squares Mean)
Placebo10.29
Eszopiclone12.49
Zopiclone13.48

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Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionnumber of substitutions (Least Squares Mean)
7.5 hours post-dose, n=89, 87, 908 hours post-dose, n=87, 84, 888.5 hours post-dose, n=89, 87, 909 hours post-dose, n=88, 87, 909.5 hours post-dose, n=88, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=86, 85, 8811 hours post-dose, n=88, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone64.366.267.064.866.968.069.567.867.8
Placebo67.970.270.467.969.970.871.570.668.7
Zopiclone63.065.266.063.866.267.367.467.368.0

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Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionnumber of substitutions (Least Squares Mean)
7.5 hours post-dose, n=89, 87, 908 hours post-dose, n=87, 84, 888.5 hours post-dose, n=89, 87, 909 hours post-dose, n=88, 87, 909.5 hours post-dose, n=88, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=86, 85, 8811 hours post-dose, n=88, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone64.766.567.465.267.268.269.768.168.0
Placebo68.270.470.668.170.270.971.870.969.0
Zopiclone63.465.666.364.266.567.667.867.668.3

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Sedation Score, as Assessed by the Linear Analogue Rating Scales

"The Linear Analogue Rating Scale (LARS) is used as a measure of the subjective effects of psychoactive drugs. Participants mark a series of 10 cm (100 unit line) analogue scales (1-100, 100 = most impaired) relating to dizzy, clumsy, anxious, relaxed, tired, drowsy, alert, energetic, sad, and depressed, indicating their present feeling with regard to a mid-point, representing their usual state of mind before treatment began. The higher the score, the more impaired the participant feels. The Tiredness, Alertness, Energy, and Drowsiness scores are averaged to derive an overall Sedation score." (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionpoints on a scale (Least Squares Mean)
7.5 hours post-dose, n=89, 87, 908 hours post-dose, n=89, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 9011 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone54.8756.4054.3954.9355.3954.6853.7751.4949.41
Placebo54.2154.5454.0753.6353.8453.9851.7751.4749.02
Zopiclone57.0059.2156.9356.0155.9055.7355.3152.7951.24

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Mood Score, as Assessed by the Linear Analogue Rating Scales

"Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Anxiety, Depression, Relaxed, and Sadness scores are averaged to derive an overall Mood score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired." (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionpoints on a scale (Least Squares Mean)
7.5 hours post-dose, n=89, 87, 908 hours post-dose, n=89, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 9011 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone48.1348.4248.4247.6747.8948.2548.7247.0747.09
Placebo47.7549.1948.8848.4848.3047.9847.5747.4545.63
Zopiclone48.0349.1148.3048.6147.5448.2848.4747.9046.08

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Mean Tracking Error (MTE) Assessed During the CTT

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) . The CTT is a task (8 minute duration) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the MTE, the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionpixels (Least Squares Mean)
7.5 hours post-dose8 hours post-dose8.5 hours post-dose9 hours post-dose9.5 hours post-dose10 hours post-dose10.5 hours post-dose11 hours post-dose11.5 hours post-dose
Eszopiclone12.8012.7212.5413.0013.5012.8511.3810.8610.06
Placebo10.209.7010.0811.0210.4410.129.4810.559.18
Zopiclone13.0713.1512.9314.8113.5512.5311.8411.6510.30

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CTT Mean Reaction Time

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) A further outcome derived from the CTT is a peripheral awareness task where the participant responds to a stimulus presented in the periphery of vision, while simultaneously attending to the tracking test. The mean reaction time, in milliseconds, to these stimuli over the trial period is taken as the response measure for this component of the divided attention task. A lower mean reaction time is indicative of better peripheral awareness. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionmilliseconds (Least Squares Mean)
7.5 hours post-dose, n=89, 87, 908 hours post-dose, n=88, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 9011 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone791.99787.41793.18802.53793.69778.09774.06760.29750.79
Placebo746.88744.90757.72760.11763.65756.67765.98762.43745.26
Zopiclone806.31799.53797.92811.11789.63792.00779.80765.56766.44

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Critical Flicker Fusion Test-Overall Threshold

Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four ascending and four descending presentations of the CFF give the overall threshold frequency in hertz. (NCT00699608)
Timeframe: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)

,,
Interventionhertz (Least Squares Mean)
7.5 hours post-dose, n=88, 87, 908 hours post-dose, n=89, 87, 908.5 hours post-dose, n=89, 87, 909 hours post-dose, n=89, 87, 909.5 hours post-dose, n=89, 87, 9010 hours post-dose, n=89, 87, 9010.5 hours post-dose, n=89, 87, 8911 hours post-dose, n=89, 87, 9011.5 hours post-dose, n=89, 87, 90
Eszopiclone29.5729.1128.8628.7928.9028.9529.0029.0729.50
Placebo29.8229.4129.3629.1029.1929.2029.3829.3729.46
Zopiclone29.4529.0028.8828.9628.9029.0229.1429.1429.53

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Mean Standard Deviation of Speed (SDS) in the Highway Drive Test

Mean standard deviation of speed (SDS) is a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed are recorded and analyzed. (NCT01106859)
Timeframe: 3-9 hours post dose

Interventionkilometers/hour (Least Squares Mean)
Zolpidem 4 Hours Prior1.98
Zolpidem 3 Hours Prior1.91
Zopiclone1.99
Placebo1.83

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Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.0 cm SDLP Threshold

SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 2.0 cm threshold. A neutral driving performance shows a difference of SDLP >= 2.0 cm and <= -2.0 cm when compared to placebo. A worse performance is when the difference of SDLP > 2.0 cm, and an improved performance is when the difference of SDLP < -2.0 cm. (NCT01106859)
Timeframe: 3-9 hours post dose

,,
Interventionparticipants (Number)
ImpairedNeutralImproved
Zolpidem 3 Hours Prior13252
Zolpidem 4 Hours Prior6331
Zopiclone19210

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Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 3.5 cm SDLP Threshold

SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 3.5 cm threshold. A neutral driving performance shows a difference of SDLP >= 3.5 cm and <= -3.5 cm when compared to placebo. A worse performance is when the difference of SDLP > 3.5 cm, and an improved performance is when the difference of SDLP < -3.5 cm. (NCT01106859)
Timeframe: 3-9 hours post dose

,,
Interventionparticipants (Number)
ImpairedNeutralImproved
Zolpidem 3 Hours Prior7330
Zolpidem 4 Hours Prior2380
Zopiclone14260

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Probability of Differences From Placebo Exceeding The 2.0 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

"This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of <.001 are listed in the data table as 0.000.~A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance." (NCT01106859)
Timeframe: 3-9 hours post dose

,,,
Interventionproportion (Number)
Probability - impairedProbability - improved
PlaceboNANA
Zolpidem 3 Hours Prior0.3250.050
Zolpidem 4 Hours Prior0.1500.025
Zopiclone0.4750.000

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Probability of Differences From Placebo Exceeding The 2.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

"This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of <.001 are listed in the data table as 0.000.~A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance." (NCT01106859)
Timeframe: 3-9 hours post dose

,,,
Interventionproportion (Number)
Probability - impairedProbability - improved
PlaceboNANA
Zolpidem 3 Hours Prior0.2500.025
Zolpidem 4 Hours Prior0.1250.025
Zopiclone0.4500.000

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Probability of Differences From Placebo Exceeding The 3.5 cm Threshold in Standard Deviation of Lateral Position (SDLP) Following Administration of Active Therapy

"This table represents the probability of driving performance changes summarized in the previous table. It answers the question: What is the chance that # participants out of the total number of participants had better (or worse) driving performance? Probability values of <.001 are listed in the data table as 0.000.~A symmetry analysis was conducted for the probability of difference in mean SDLP (treatment) - mean SDLP (placebo) exceeding thresholds. Statistically significant asymmetries indicate a decrement in driving performance." (NCT01106859)
Timeframe: 3-9 hours post dose

,,,
Interventionproportion (Number)
Probability - impairedProbability - improved
PlaceboNANA
Zolpidem 3 Hours Prior0.1750.000
Zolpidem 4 Hours Prior0.0500.000
Zopiclone0.3500.000

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Summary of Participants With Treatment Emergent Adverse Experiences (TEAEs)

Adverse Events were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe) and relatedness (summarized as 'unrelated' and 'related') to study treatment. Also included are counts of participants with serious AEs, AEs leading to discontinuation of study treatment, and deaths. (NCT01106859)
Timeframe: Day 1 -6 weeks

,,,
Interventionparticipants (Number)
At least one TEAETEAE graded as mildTEAE graded as moderateTEAE graded as severeUnrelatedRelatedAt least one serious AEDiscontinued study medication due to AEDeath
Placebo440013000
Zolpidem 3 Hours Prior550023000
Zolpidem 4 Hours Prior541032000
Zopiclone660042000

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Number of Participants Whose Standard Deviation of Lateral Position (SDLP) Following Active Treatment As Compared to Placebo In Relation To The 2.5 cm SDLP Threshold

SDLP was measured by an infrared camera mounted on the car's roof during a highway driving test. Lateral position of the car relative to the left lane boundary was recorded. The data summarizes the number of participants whose driving performance was worse, neutral or improved as compared to placebo at the 2.5 cm threshold. A neutral driving performance shows a difference of SDLP >= 2.5 cm and <= -2.5 cm when compared to placebo. A worse performance is when the difference of SDLP > 2.5 cm, and an improved performance is when the difference of SDLP < -2.5 cm. (NCT01106859)
Timeframe: 3-9 hours post dose

,,
Interventionparticipants (Number)
ImpairedNeutralImproved
Zolpidem 3 Hours Prior10291
Zolpidem 4 Hours Prior5341
Zopiclone18220

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Mean Standard Deviation of Lateral Position (SDLP) in the Highway Driving Test

Standard deviation of lateral position (SDLP) in a highway-driving lane is a surrogate measure for driving performance. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed. (NCT01106859)
Timeframe: 3-9 hours post dose

Interventioncentimeters (Least Squares Mean)
Zolpidem 4 Hours Prior16.7
Zolpidem 3 Hours Prior17.3
Zopiclone18.3
Placebo15.9

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Use of Zopiclone (Night Sedation)

"The number of patients taking zopiclone during their stay. Data was taken from the Electronic patient record and was not available for any patient not discharged at the end of the study (one in each group).~NOT the original intention of measuring the total dose of zopiclone taken during the admission will be recorded; this is available from the electronic drug chart used in the hospital" (NCT02732912)
Timeframe: From date of admission to date of discharge, up to 90 days

InterventionParticipants (Count of Participants)
Control2
Eye Mask and Ear Plugs3

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SleepSure (Questionnaire). A Short Questionnaire of the Quality and Quantity of Sleep, and Use of Aids.

SleepSure is a short questionnaire which asks the patient to rate their sleep using a 1-10 numerical rating scale for eight items covering the quality of their sleep (e.g. difficulty getting to sleep, interruptions). Two additional questions recorded the use of aids. It takes no more that 2-3 minutes to complete. The eight numerical rating scores are summed and divided by 8 to give a score from 1 (very good sleep) to 10 (very poor sleep). (NCT02732912)
Timeframe: At end of first night in hospital after recruitment (i.e. the next morning)

Interventionunits on a scale (Mean)
Control5.09
Eye Mask and Ear Plugs6.33

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Number of Falls

The number of falls, if any, will be extracted from the hospital incident recording system for the patient at the time of discharge. The data will be reported simply as the number of patients experiencing a fall; not the total number of falls experienced by the patients who had a fall. The data were taken from the electronic patient records and were not available for patients (n = 2) still in hospital at the time of discharge. (NCT02732912)
Timeframe: From date of admission to date of discharge, up to 90 days

InterventionParticipants (Count of Participants)
Control0
Eye Mask and Ear Plugs0

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Length of Stay

Time in days from admission to discharge from hospital (not from ward). These data were derived from the hospital administration data-base. (NCT02732912)
Timeframe: From date of admission to date of discharge, up to 90 days

Interventiondays (Mean)
Control4.83
Eye Mask and Ear Plugs3.67

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Amount of Awakenings

Number of awakenings between sleep onset and final morning awakening (NCT03339583)
Timeframe: once at baseline assessment

Interventionawakenings (Mean)
Zopiclone First, Then BBT-I13.78
BBT-I First, Then Zopiclone13.25

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N1 NREM Sleep Percentage

Percentage of Total Sleep Time (NCT03339583)
Timeframe: once at baseline assessment

Interventionpercentage of total sleep time (Mean)
Zopiclone First, Then BBT-I4.16
BBT-I First, Then Zopiclone3.70

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N2 NREM Sleep Percentage

Percentage of Total Sleep Time (NCT03339583)
Timeframe: once at baseline assessment

Interventionpercentage of time (Mean)
Zopiclone First, Then BBT-I64.19
BBT-I First, Then Zopiclone62.58

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N3 NREM Sleep Percentage

Percentage of Total Sleep Time (NCT03339583)
Timeframe: once at baseline assessment

Interventionpercentage of total sleep time (Mean)
Zopiclone First, Then BBT-I17.52
BBT-I First, Then Zopiclone16.39

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REM Sleep Percentage

Percentage of Total Sleep Time (NCT03339583)
Timeframe: once at baseline assessment

Interventionpercentage of total sleep time (Mean)
Zopiclone First, Then BBT-I14.1
BBT-I First, Then Zopiclone17.0

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Sleep Latency

time period from bedding to sleep onset (NCT03339583)
Timeframe: once at baseline assessment

Interventionminutes (Mean)
Zopiclone First, Then BBT-I38.53
BBT-I First, Then Zopiclone54.5

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Toronto Alexithymia Scale (TAS-20)

Degree of alexithymia evaluated by Toronto Alexithymia scale (20 questions) Measure Description: 0-100 scores. higher values represent worse outcome (NCT03339583)
Timeframe: once at baseline assessment

Interventionscores on a scale (Mean)
Zopiclone First, Then BBT-I49.83
BBT-I First, Then Zopiclone49.33

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Insomnia Severity Index

self reported insomnia symptoms severity by Insomnia severity index . Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28). (NCT03339583)
Timeframe: For BBT-I-first group: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/Month 1); For zopiclone-first group: after washout period (Day 28/Week 4/Month 1) after second treatment course (Day 42/Week 6/Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationFirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group18.613.114.312.113.1
Zopiclone First Group18.914.016.112.812.7

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Dysfunctional Beliefs About Sleep Scale

questionnaire assessing sleep related cognitions in 16 item rated on a 10-point Likert scale. Minimum score is 0, maximum score is 160 points. Higher total score represents more intensive disfunctional beliefs (NCT03339583)
Timeframe: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationFirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group105.283.884.7684.562.8
Zopiclone First Group93.296.4103.689.292.0

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Beck Depression Inventory

21-item questionnaire assessing (on 4-point Likert scales) the intensity of depressive symptoms in the past week. Minimum score 0, maximum score 63 points. Higher total score represents more severe depressive symptoms (NCT03339583)
Timeframe: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationfirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group11.58.48.49.29.0
Zopiclone First Group9.39.49.88.57.4

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Wake After Sleep Onset

total duration of all periods of wakefulness between sleep onset and final awakening in the morning (NCT03339583)
Timeframe: once at baseline assessment

Interventionminutes (Mean)
Zopiclone First, Then BBT-I102.39
BBT-I First, Then Zopiclone104.75

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Total Sleep Time

total sleep episode minus wake time (NCT03339583)
Timeframe: once at baseline assessment

Interventionhours (Mean)
Zopiclone First, Then BBT-I5.72
BBT-I First, Then Zopiclone5.51

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Sleep Efficiency

Prercentage of Total Bed Time (NCT03339583)
Timeframe: once at baseline assessment

Interventionpercentage of polysomnogram time (Mean)
Zopiclone First, Then BBT-I64.68
BBT-I First, Then Zopiclone63.29

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Trait Anxiety Subscale (STAI)

STAI is a 2-part questionnaire assessing state (situational) and trait anxiety. Trait anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for each subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms (NCT03339583)
Timeframe: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationFirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group48.748.348.646.346.3
Zopiclone First Group48.348.349.348.548.8

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State Anxiety Subscale (STAI)

State trait anxiety scale is a 2-part questionnaire assessing state (situational) and trait anxiety. State anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms (NCT03339583)
Timeframe: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationFirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group45.143.845.545.146.9
Zopiclone First Group43.244.344.544.044.2

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Sleep Hygiene Index

questionnaire assessing sleep related behavior in 13 item rated on a 5-point Likert scale.Minimum score 13 points and maximum score 65 points. Higher total score represents worse sleep hygiene (NCT03339583)
Timeframe: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationFirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group26.824.024.724.723.8
Zopiclone First Group25.225.025.524.325.2

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Pittsburgh Sleep Quality Index

19-item questionnaire evaluating sleep quality over the past month. The first 4 items are open questions, items 5 to 19 are rated on a 4-point Likert scale. A total score range from 0 to 21. A score > 5 suggests poor sleep quality. (NCT03339583)
Timeframe: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

,
Interventionunits on a scale (Mean)
Baseline/initial examinationFirst treatment courseAfter washoutSecond treatment courseAfter follow-up
BBT-I First Group13.410.511.310.811.2
Zopiclone First Group11.911.312.711.711.1

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