generation run 2026-05-09
66 min completedmodel pipeline-v5plan not recordedrun/9d3e1038…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- taper_protocol_generic
- no_dedicated_taper_manual
- cross_taper_not_documented
Reproduce
- inputs
- 46 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
25 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | PMID 15806735 | 1 | 1 | — |
| 2 | WebSearch | zopiclone legal status scheduling UK US Canada Australia controlled substance | 10 | 2 | — |
| 3 | PubChem | zopiclone | 1 | 1 | — |
| 4 | OpenAlex | zopiclone GABA receptor pharmacology | 10 | 2 | — |
| 5 | ClinicalTrials.gov | zopiclone insomnia sleep | 10 | 2 | — |
| 6 | PubMed | zopiclone erythromycin carbamazepine CYP3A4 drug interaction | 2 | 2 | — |
| 7 | PubMed | zopiclone pharmacokinetics bioavailability half-life metabolism | 5 | 5 | — |
| 8 | PubMed | zopiclone GABA-A receptor subunit selectivity binding affinity | 2 | 2 | — |
| 9 | PubMed | zopiclone dependence withdrawal abuse potential | 10 | 4 | — |
| 10 | PubMed | zopiclone driving impairment psychomotor next-day residual effects | 6 | 5 | — |
| 11 | PubMed | zopiclone bitter taste metallic taste side effect | 6 | 3 | — |
| 12 | PubMed | zopiclone pharmacology GABA receptor mechanism of action | 10 | 2 | — |
| 13 | PubMed | zopiclone sleep polysomnography insomnia clinical trial | 10 | 2 | — |
| 14 | PubMed | zopiclone complex sleep behavior sleepwalking | 3 | 2 | — |
| 15 | PubMed | PMID 12751920 zopiclone drug interactions | 1 | 1 | — |
| 16 | PubMed | PMID 23404347 forensic toxicology Z-drugs | 1 | 1 | — |
| 17 | PubMed | zopiclone placebo controlled randomized insomnia efficacy | 8 | 3 | — |
| 18 | WebSearch | zopiclone Australia Schedule 4 New Zealand Canada controlled drug history | 10 | 2 | — |
| 19 | OpenAlex | zopiclone dependence tolerance withdrawal benzodiazepine | 8 | 2 | — |
| 20 | PubMed | zopiclone alcohol interaction sedation CNS depressant | 2 | 1 | — |
| 21 | PubMed | zopiclone memory performance impairment psychomotor cognitive | 6 | 2 | — |
| 22 | ClinicalTrials.gov | zopiclone | 10 | 3 | — |
| 23 | PubMed/OpenAlex/WebSearch · absence | Cross-reference seed data against published sources | 0 | 0 | — |
| 24 | PubMed | zopiclone placebo randomized insomnia efficacy sleep onset | 8 | 3 | — |
| 25 | WebSearch | zopiclone history discovery 1986 Rhone-Poulenc first approval France cyclopyrrolone | 10 | 1 | — |
128 claims by section — every cited sentence, checked against its source
safety59 · 35 ok
Erythromycin enhances zopiclone sedative effects through metabolic inhibitionsupported
CYP inhibitors (ketoconazole, erythromycin, cimetidine) enhanced sedative effects. pmid:12751920
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Post-mortem forensic data include cases where zopiclone was detected at therapeutic concentrations alongside lethal concentrations of other substances, and cases where zopiclone was present at toxic concentrations (1,200 µg/L femoral blood) in fatal polydrug ingestions.supported
Post-mortem analysis revealed zopiclone at 0.043 mg/L in peripheral blood — within therapeutic range — alongside toxic mitragynine and 7-hydroxymitragynine concentrations. j.forsciint.2014.10.025
Post-mortem forensic data include cases where zopiclone was detected at therapeutic concentrations alongside lethal concentrations of other substances, and cases where zopiclone was present at toxic concentrations (1,200 µg/L femoral blood) in fatal polydrug ingestions.supported
Zopiclone detected at 1,200 mcg/L in femoral blood at toxic concentrations alongside tramadol, propranolol, bromazepam, and citalopram. ftd.0000000000001150
EudraVigilance pharmacovigilance analysis identified 9,283 zopiclone-associated adverse drug reactions across 6,246 unique patients in the European database, with zopiclone most frequently involved in overdose adverse drug reactions among the three Z-drugs studied.supported
EudraVigilance data: 9,283 zopiclone adverse drug reactions among 6,246 unique patients. Zopiclone... was most involved in overdose adverse drug reactions. pyz007
Published polysomnographic data show no detrimental effects on respiratory indices at the therapeutic 7.5 mg dosesupported
No respiratory changes. pmid:9214191
Claim in safety — inconclusiveinconclusiveworking →
A case of acute liver injury was published for eszopiclone in a patient with pre-existing chronic liver disease, suggesting that hepatic injury is possible but rare with the active enantiomersupported
Case report of acute liver injury following eszopiclone treatment in patient with chronic hepatitis B. First report of liver enzyme elevation or severe liver injury caused by eszopiclone. md.0000000000026243
CYP3A4-dependent metabolism means hepatic impairment significantly alters drug exposure.supported
In liver insufficiency: prolonged t1/2 8.4h. pmid:3438645
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Complex sleep behaviors represent a distinct safety concern: patients may engage in potentially dangerous activities (driving, cooking, eating) during incomplete arousal states with no subsequent memory of the eventssupported
Post-marketing analysis of complex sleep behaviors (CSBs) resulting in serious injuries including death associated with Z-drugs. pds.5004
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Irritability, emotional lability, and paradoxical behavioral disinhibition have been reported, with higher incidence in elderly patientssupported
3 participants had intervention interrupted due to intense daytime sedation and worsened agitation with wandering. s41386-021-01191-3
Broader epidemiological data associate long-term hypnotic use with increased depression and mortality risk, though causality is not established.supported
Review of hypnotic risks including excess mortality, overdose deaths, quiet deaths at night, suicides, infections, cancer, depression, automobile crashes, falls. f1000research.8729.1
A 17-week sleep laboratory study demonstrated sustained efficacy without measurable tolerance, and long-term eszopiclone data extend to 12 monthssupported
17-week continuous study with 6 chronic insomniacs... Drug maintained effectiveness with prolonged use. pmid:3365634
Claim in safety — inconclusiveinconclusiveworking →
Cross-tolerance with benzodiazepines is pharmacologically expected and confirmed, given the shared binding site at GABA-A receptors.supported
Binding thought to occur to benzodiazepine receptor complex. pmid:2874974
Claim in safety — inconclusiveinconclusiveworking →
Case reports document dependence in individual patients, and EudraVigilance surveillance data indicate zopiclone presents dependence risk equivalent to zolpidemsupported
Cases of abuse and dependence are being reported in literature. fpsyt.2025.1592065
Case reports document dependence in individual patients, and EudraVigilance surveillance data indicate zopiclone presents dependence risk equivalent to zolpidemsupported
Zopiclone presented same dependence risk as zolpidem. pyz007
Abuse and misuse have been documented in addiction service populationssupported
Review examining dependence/abuse potential of zopiclone: recommended use problems, driving impairment, dependence issues, recreational misuse. jrs-140633
Abuse and misuse have been documented in addiction service populationssupported
Review to determine whether zopiclone could be an agent for abuse. pmid:18077750
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — not_supportednot supportedworking →
Claim in safety — inconclusiveinconclusiveworking →
Comparative data confirm that zopiclone's benefits do not persist after stopping treatment — in contrast to CBT-I, whose benefits are maintained — with rebound symptoms emerging upon cessationsupported
After stopping treatment, CBT-I benefits lasted longer than zopiclone. jnevro20171174248-55
Gradual dose taper is recommended to mitigate withdrawal severity.supported
Slow tapering recommended. Z-drugs (including zopiclone) have similar dependence issues. j.1365-2125.2012.04418.x
Claim in safety — inconclusiveinconclusiveworking →
Erythromycin enhances zopiclone sedative effects through metabolic inhibitionsupported
Metabolic drug interactions with erythromycin, trimipramine, and carbamazepine. pmid:10379424
Azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin), nefazodone, ritonavir, and cimetidine similarly inhibit zopiclone metabolism, potentially requiring dose reductionsupported
Clinically important CYP3A4 inhibitors include erythromycin, ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, grapefruit juice. pmid:10668858
Azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin), nefazodone, ritonavir, and cimetidine similarly inhibit zopiclone metabolism, potentially requiring dose reductionsupported
CYP inhibitors (ketoconazole, erythromycin, cimetidine) enhanced sedative effects. pmid:12751920
Grapefruit juice may inhibit CYP3A4-mediated metabolism.supported
Clinically important CYP3A4 inhibitors include erythromycin, ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, grapefruit juice. pmid:10668858
Rifampicin significantly accelerates metabolism, reducing sedative effectssupported
CYP inducers (rifampicin) significantly decreased sedative effects. pmid:12751920
Claim in safety — inconclusiveinconclusiveworking →
Carbamazepine produces a similar interaction through metabolic induction.supported
Metabolic drug interactions with erythromycin, trimipramine, and carbamazepine. pmid:10379424
The alcohol interaction is pharmacodynamic rather than pharmacokinetic: zopiclone's pharmacokinetic parameters are not substantially altered by concurrent alcohol, but CNS depressant effects are clearly additive and potentially dangeroussupported
Alcohol enhanced and prolonged effects of both hypnotics (additive interaction). pmid:2201724
The alcohol interaction is pharmacodynamic rather than pharmacokinetic: zopiclone's pharmacokinetic parameters are not substantially altered by concurrent alcohol, but CNS depressant effects are clearly additive and potentially dangeroussupported
Ethanol: additive sedative effects without pharmacokinetic alteration. pmid:12751920
Other CNS depressants — opioids, benzodiazepines, antipsychotics, sedating antihistamines, and sedating antidepressants — produce additive sedation and respiratory depression risk through the same pharmacodynamic mechanism.partially supported
CYP3A4 inhibitors cause excessive sedation with non-BZD hypnotics including zopiclone. pmid:10668858
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
A pharmacokinetic interaction with trimipramine has been documented: zopiclone decreased trimipramine bioavailability by approximately 26.6%, though the clinical significance of this interaction is uncertain.supported
Zopiclone/trimipramine interaction: zopiclone decreased trimipramine bioavailability by 26.6%. pmid:6743780
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Additive sedation and respiratory depression with alcohol, opioids, benzodiazepines, and other sedating agents substantially increases overdose risk.supported
Alcohol enhanced and prolonged effects of both hypnotics (additive interaction). pmid:2201724
Additive sedation and respiratory depression with alcohol, opioids, benzodiazepines, and other sedating agents substantially increases overdose risk.supported
Ethanol: additive sedative effects without pharmacokinetic alteration. pmid:12751920
Breastfeeding is contraindicated due to zopiclone's excretion in breast milk at a milk/plasma ratio of approximately 0.80.supported
Milk/plasma ratio ~0.80 in nursing mothers. pmid:6669634
Severe hepatic impairment requires mandatory dose reduction to 3.5 mg, as bioavailability increases to ~97% and the elimination half-life extends to ~8.4 hours in this population.supported
In liver insufficiency: prolonged t1/2 8.4h. Recommends dose reduction from 7.5mg to 3.5mg/day for elderly with liver insufficiency. pmid:3438645
Elderly patients (over 70 years) require dose reduction to 3.75 mg due to significantly altered pharmacokinetics — bioavailability increases up to ~168% and half-life extends to ~8.1 hours — combined with elevated falls risk and cognitive vulnerability.partially supported
In elderly over 74: half-life up to 8.1h. Recommends dose reduction from 7.5mg to 3.5mg/day for elderly with liver insufficiency. pmid:3438645
Elderly patients (over 70 years) require dose reduction to 3.75 mg due to significantly altered pharmacokinetics — bioavailability increases up to ~168% and half-life extends to ~8.1 hours — combined with elevated falls risk and cognitive vulnerability.supported
Adverse cognitive events 4.78x more common; adverse psychomotor events 2.61x more common... In people over 60, benefits may not justify increased risk. bmj.38623.768588.47
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Driving and machinery operation should be avoided for at least 8–10 hours following a 7.5 mg oral dose, given documented residual psychomotor impairment persisting up to 10 hours.supported
Zopiclone 7.5mg impaired driving ability as measured 4h and up to 10h after administration. pmid:12404558
Claim in safety — inconclusiveinconclusiveworking →
pharmacology21 · 19 ok
CYP3A4 is the principal cytochrome P450 isoform involved in hepatic metabolism.supported
CYP3A4 plays important role. pmid:10379424
Zopiclone is a positive allosteric modulator (PAM) of ionotropic GABA-A receptors, binding at the benzodiazepine site located at the interface of the α and γ₂ subunitssupported
Binding thought to occur to benzodiazepine receptor complex. pmid:2874974
Zopiclone and its active S-enantiomer show preferential interaction with omega-1 (α1-containing) receptors over omega-2 (α2/α3-containing) subtypes, though this selectivity is substantially less pronounced than that of zolpidempartially supported
Interact preferentially with omega-1 (alpha-1) receptors vs omega-2 for BZDs. pmid:12608888
Functional electrophysiology studies demonstrated that racemic zopiclone and the S-desmethylzopiclone metabolite (SEP-174559) potentiate GABA-A currents across α1-, α2-, and α3-containing assemblies without meaningful subtype selectivity, and that potentiation strictly requires the γ2 subunit.supported
Not selective between alpha1, alpha2, alpha3-bearing receptors. Requires gamma2 subunit. These effects shared with parent compound racemic zopiclone. pmid:12130723
Structural analysis of eszopiclone at the benzodiazepine binding pocket revealed a binding mode dependent on specific hydrogen bonds at γ2 loops D and E and α1 loops A, B, and C — mechanistically distinct from zolpidem, which relies primarily on hydrophobic shape complementarity within the pocket.partially supported
Mutations in gamma2 loop E and alpha1 loop C differentially affected ligand affinity. Eszopiclone docking: single model stabilized by several hydrogen bonds. Zolpidem: three orientations with few polar interactions. jm800889m
Secondary pharmacological actions include noncompetitive inhibition of nicotinic acetylcholine (nACh) receptors and inhibition of NMDA receptor currents at micromolar concentrations in vitrosupported
Also inhibits nicotinic acetylcholine receptors (noncompetitively) and NMDA receptor currents. These effects shared with parent compound racemic zopiclone. pmid:12130723
Claim in pharmacology — inconclusiveinconclusiveworking →
Zopiclone is rapidly absorbed following oral administration, reaching peak plasma concentrations (T_max) within 0.5–1 hour in healthy young adultssupported
After oral administration, zopiclone is rapidly absorbed, with a bioavailability of approximately 80%. pmid:8787948
Absolute oral bioavailability is approximately 77%, reflecting a first-pass hepatic extraction of 20–25%supported
First-pass effect of 20%, absolute bioavailability 77%. pmid:3438645
Protein binding ranges from 45–80% across published studies.supported
Plasma protein binding 45-80%. pmid:8787948
Protein binding ranges from 45–80% across published studies.supported
Plasma protein binding ~45%. pmid:6669634
Claim in pharmacology — inconclusiveinconclusiveworking →
Hepatic metabolism proceeds through three primary routes: (1) decarboxylation, accounting for greater than 50% of the dose and producing CO₂ exhaled via the lungs; (2) N-demethylation, yielding the inactive N-desmethylzopiclone metabolite; and (3) N-oxidation, producing the pharmacologically active N-oxide metabolitesupported
Metabolites: inactive N-demethylated derivative and active N-oxide metabolite. ~50% decarboxylated and exhaled. pmid:8787948
Hepatic metabolism proceeds through three primary routes: (1) decarboxylation, accounting for greater than 50% of the dose and producing CO₂ exhaled via the lungs; (2) N-demethylation, yielding the inactive N-desmethylzopiclone metabolite; and (3) N-oxidation, producing the pharmacologically active N-oxide metabolitesupported
Major metabolic routes: decarboxylation >50%, N-demethylation and N-oxidation >30%. pmid:6669634
CYP3A4 is the principal cytochrome P450 isoform involved in hepatic metabolism.partially supported
Zopiclone biotransformed by multiple CYP isozymes in addition to CYP3A4. pmid:12751920
The elimination half-life in healthy young adults is 3.5–6.5 hours, with controlled studies reporting a mean of approximately 5.1 hourssupported
Terminal elimination half-life 3.5-6.5 hours. pmid:8787948
The elimination half-life in healthy young adults is 3.5–6.5 hours, with controlled studies reporting a mean of approximately 5.1 hourssupported
Half-life 5.1h. pmid:3438645
The elimination half-life in healthy young adults is 3.5–6.5 hours, with controlled studies reporting a mean of approximately 5.1 hourssupported
Elimination half-life 3.8h. pmid:6743780
Less than 7% of the dose is excreted unchanged in urine; total body clearance is approximately 300 mL/min, with renal clearance contributing only ~10 mL/minsupported
Total body clearance 300ml/min. <7-10% excreted unchanged. pmid:6669634
Zopiclone is detectable in saliva, with the characteristic bitter taste appearing at approximately 24 minutes post-dose when saliva concentrations reach ~50 ng/mLpartially supported
Bitter taste reported at 24 min post-dose. pmid:6743780
The compound is excreted in breast milk with a milk/plasma ratio of approximately 0.80.supported
Milk/plasma ratio ~0.80 in nursing mothers. pmid:6669634
comparative-pharmacology11 · 8 ok
Zopiclone 7.5 mg produces measurable psychomotor and cognitive impairment lasting up to 10 hours post-dose, compared to approximately 5 hours for zolpidem 10 mgsupported
Zopiclone 7.5mg showed significant detrimental residual effects on psychomotor/cognitive functions up to 10h after dose administration. Zolpidem 10mg up to 5h. pmid:12404558
Zopiclone 7.5 mg produces measurable psychomotor and cognitive impairment lasting up to 10 hours post-dose, compared to approximately 5 hours for zolpidem 10 mgsupported
Driving impairment occurs with zopiclone up to 10h after dose. s13181-013-0294-y
EudraVigilance pharmacovigilance data show that zopiclone presents the same dependence risk as zolpidem but is more frequently involved in overdose adverse drug reactions among the three Z-drugs.supported
Zopiclone presented same dependence risk as zolpidem but was most involved in overdose adverse drug reactions. pyz007
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — not_supportednot supportedworking →
Zolpidem demonstrates marked preference for α1-containing (omega-1) receptors, while zopiclone modulates α1-, α2-, and α3-containing assemblies without meaningful selectivitysupported
Not selective between alpha1, alpha2, alpha3-bearing receptors. These effects shared with parent compound racemic zopiclone. pmid:12130723
Zolpidem demonstrates marked preference for α1-containing (omega-1) receptors, while zopiclone modulates α1-, α2-, and α3-containing assemblies without meaningful selectivitypartially supported
Interact preferentially with omega-1 (alpha-1) receptors vs omega-2 for BZDs. pmid:12608888
Structurally, the two drugs use fundamentally different binding modes at the benzodiazepine pocket: zopiclone/eszopiclone relies on hydrogen bonding at specific α1 and γ2 loop residues, while zolpidem relies on hydrophobic shape recognition.supported
Eszopiclone docking: single model stabilized by several hydrogen bonds. Zolpidem: three orientations with few polar interactions. Suggests eszopiclone relies on specific residue interactions while zolpidem relies on shape recognition. jm800889m
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Zopiclone preserves slow-wave sleep architecture more effectively than benzodiazepine hypnotics, which typically suppress both SWS and REM sleepsupported
REM sleep substantially unaffected; slow wave sleep unaffected or increased. pmid:2201726
A meta-analysis of sedative hypnotics in older people found that the risk-benefit ratio for Z-drugs (including zopiclone) was marginal in elderly populations, with meaningful increases in adverse cognitive and psychomotor events relative to placebo.supported
Adverse cognitive events 4.78x more common; adverse psychomotor events 2.61x more common; daytime fatigue 3.82x more common. In people over 60, benefits may not justify increased risk. bmj.38623.768588.47
clinical-evidence9 · 7 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
A triple-blind, placebo-controlled trial (NCT03075241) in 62 patients with Alzheimer's disease compared zopiclone 7.5 mg/day, zolpidem 10 mg/day, and placebo over 14 dayssupported
RCT in 62 AD patients (mean age 80.5 years). Zopiclone 7.5mg/day... NCT03075241. s41386-021-01191-3
A comparative study of zopiclone versus cognitive-behavioral therapy for insomnia (CBT-I) demonstrated equivalent short-term efficacy, but CBT-I benefits persisted after treatment discontinuation while zopiclone's did not — rebound insomnia followed zopiclone withdrawal.supported
Both produced similar improvement (ISI decrease ~3.6-4.9 points). After stopping treatment, CBT-I benefits lasted longer than zopiclone. jnevro20171174248-55
Claim in clinical-evidence — inconclusiveinconclusiveworking →
A 2022 Lancet network meta-analysis — the largest comparative analysis of pharmacological insomnia interventions — confirmed zopiclone's acute efficacy while noting a higher adverse event profile relative to newer agentssupported
Zopiclone more efficacious than placebo (SMD range 0.36-0.83). Zopiclone caused more dropouts due to adverse events than placebo (OR 2.00)... Zopiclone caused more dropouts than eszopiclone, daridorexant, and suvorexant. s0140-6736(22)00878-9
A sleep laboratory evaluation demonstrated sustained hypnotic effectiveness over 17 weeks of continuous use without evidence of tolerance to sleep-promoting effectssupported
17-week continuous study with 6 chronic insomniacs... Drug maintained effectiveness with prolonged use. pmid:3365634
Polysomnographic studies consistently show that zopiclone preserves or mildly increases slow-wave sleep (stages 3/4) while leaving REM sleep substantially unaffected or only mildly reducedsupported
REM sleep substantially unaffected; slow wave sleep unaffected or increased. pmid:2201726
Polysomnographic studies consistently show that zopiclone preserves or mildly increases slow-wave sleep (stages 3/4) while leaving REM sleep substantially unaffected or only mildly reducedsupported
Increased duration of sleep, stage 2, delta-sleep; decreased sleep latency. pmid:9214191
European insomnia guidelines recommend zopiclone for short-term use only, with a maximum treatment duration of 2–4 weekssupported
Benzodiazepines and BZD receptor agonists (including zopiclone) can be used for short-term treatment (≤4 weeks). jsr.14035
summary9 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The compound was placed in Schedule IV of the US Controlled Substances Act in 2005.supported
DEA places zopiclone, including its salts, isomers and salts of isomers into Schedule IV of the Controlled Substances Act. pmid:15806735
Unlike the highly α1-selective zolpidem, racemic zopiclone potentiates currents without marked selectivity between α1-, α2-, and α3-containing receptor assemblies, and requires the γ2 subunit for activitysupported
Not selective between alpha1, alpha2, alpha3-bearing receptors. Requires gamma2 subunit. These effects shared with parent compound racemic zopiclone. pmid:12130723
Claim in summary — inconclusiveinconclusiveworking →
Residual psychomotor and cognitive impairment persists up to 10 hours post-dose at the standard 7.5 mg oral dosesupported
Zopiclone 7.5mg showed significant detrimental residual effects on psychomotor/cognitive functions up to 10h after dose administration. pmid:12404558
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
pharmacokinetic-detail5 · 5 ok
Metabolic clearance decreases, resulting in elevated bioavailability (up to ~168% of the young-adult value in the oldest subjects studied), and the elimination half-life extends to approximately 8.1 hourspartially supported
In elderly over 74: half-life up to 8.1h. pmid:3438645
Severe hepatic impairment delays T_max to approximately 3.5 hours, increases bioavailability to ~97%, and prolongs the elimination half-life to ~8.4 hours due to reduced metabolic clearancepartially supported
In liver insufficiency: prolonged t1/2 8.4h. pmid:3438645
Decarboxylation is the dominant pathway in animal models, accounting for over 50% of the administered dose, with the liberated CO₂ exhaled via the lungssupported
Major metabolic routes: decarboxylation >50%. pmid:6669634
N-demethylation produces the inactive N-desmethylzopiclone metabolite, and N-oxidation yields the pharmacologically active N-oxide metabolitesupported
Metabolites: inactive N-demethylated derivative and active N-oxide metabolite. pmid:8787948
CYP3A4 is the principal cytochrome P450 isoform involved, with additional CYP enzymes contributing to metabolism but not yet individually characterized.partially supported
Zopiclone biotransformed by multiple CYP isozymes in addition to CYP3A4. pmid:12751920
history4 · 1 ok
The clinical program demonstrated comparable hypnotic efficacy to established benzodiazepines with the claimed advantages of preserved slow-wave sleep architecture and lower next-day residual sedation at the standard 7.5 mg dose.supported
Comparable efficacy to nitrazepam 5mg, flurazepam 15-30mg, triazolam 0.5mg, temazepam 20mg. Minimal next-day impairment. REM sleep substantially unaffected. pmid:2874974
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
neuroscience4 · 0 ok
receptor-pharmacology3 · 3 ok
Functional electrophysiology data demonstrated that racemic zopiclone and the S-desmethylzopiclone metabolite potentiate GABA-evoked currents across α1β2γ2, α2β2γ2, and α3β2γ2 receptor configurations without significant subtype selectivitysupported
Not selective between alpha1, alpha2, alpha3-bearing receptors. Requires gamma2 subunit. These effects shared with parent compound racemic zopiclone. pmid:12130723
The potentiation is strictly γ2-dependent: no modulation occurs at receptors lacking the γ2 subunitsupported
Requires gamma2 subunit. pmid:12130723
At micromolar concentrations in vitro, zopiclone and S-desmethylzopiclone noncompetitively inhibit nicotinic acetylcholine receptor currents and reduce NMDA receptor-mediated currentssupported
Also inhibits nicotinic acetylcholine receptors (noncompetitively) and NMDA receptor currents. These effects shared with parent compound racemic zopiclone. pmid:12130723
chemistry2 · 2 ok
Zopiclone is the prototypical member of the cyclopyrrolone class, a family of heterocyclic compounds structurally unrelated to benzodiazepines, barbiturates, or the imidazopyridine scaffold shared by zolpidemsupported
Zopiclone is the first of the cyclopyrrolones, a new class of psychotherapeutic agents. pmid:2874974
The carboxylate linkage is metabolically labile, providing the primary site for hepatic decarboxylation — the dominant metabolic route, accounting for over 50% of the administered dose in animal models.supported
Major metabolic routes: decarboxylation >50%, N-demethylation and N-oxidation >30%. pmid:6669634
botanical-overview1 · 0 ok
Claim in botanical-overview — inconclusiveinconclusiveworking →