Effects Of Zopiclone Research Articles

Next-day effects of zopiclone

Next-day effects of zopiclone

P0044 Effects of zopiclone and zolpidem in elderly hypertensive patients with chronic insomnia

P0044 Effects of zopiclone and zolpidem in elderly hypertensive patients with chronic insomnia

Effects of zopiclone on visual event-related potentials: Influences of emotional affects

Effects of zopiclone on visual event-related potentials: Influences of emotional affects

Effects of zopiclone on blood glucose level, serum lipid concentration and clot lysis time in normoglycemic and normolipidemic rats.

In normoglycemic and normolipidemic rats the i.p. injection of zopiclone induced an acceleration of fibrinolysis in a dose-dependent bell shaped manner and various changes of the blood glucose level. Total lipids, total cholesterol and triglyceride serum levels remained unaffected by doses of 1.25, 2.5 and 15.0 mg/kg, with the exception of the medium dose (5.0 mg/kg) and the next dose (10.0 mg/kg) which lowered them very significantly.

Double-blind, placebo-controlled study comparing effects of zopiclone and temazepam on cognitive functioning of insomniacs

The purpose of this study was to compare the cognitive effect of two medications frequently prescribed to patients suffering from insomnia. Using a double-blind design, we evaluated three parallel groups of 20 insomniac patients treated over a period of 3 weeks with zopiclone, temazepam and placebo, respectively. Our hypothesis was that the impact of zopiclone 7.5 mg/day on cognitive functioning would be minimal 12 h after administration and that temazepam 30 mg/day would affect explicit memory, as is the case with other benzodiazepines. Patients were assessed at baseline following a 1-week, single-blind placebo-intake period, and again at the end of each of the 3 weeks of the comparative phase. Then, in order to estimate the severity and duration of potential rebound insomnia, patients were again assessed following another 1-week, single-blind placebo-washout period at the end of the 3 weeks of treatment. The overall duration of the study for each patient was thus 5 weeks. The instruments of measure used were the Hamilton scale for anxiety, daily self-rating questionnaire for assessment of sleep onset, duration and quality, and two large batteries of psychometric tests. The first of these batteries assessed memory and included span tests for short-term memory, cued recall tasks for long-term explicit memory, and a word-completion task for implicit memory; the second measured attention and concentration through the assessment of alertness, sustained attention and divided attention. The sleep and anxiety results obtained confirm the findings of previous research. Zopiclone and temazepam possess a clinically significant hypnotic activity, with no rebound insomnia or anxiety, during the week of drug withdrawal. The results indicate that the two hypnotic drugs studied have little impact on cognitive functioning. We can therefore conclude that at the doses administered over the 3 weeks, the two hypnotic drugs in question are relatively safe and efficacious in the treatment of insomnia and enable patients to enjoy a good quality of life. Copyright © 1999 John Wiley & Sons, Ltd.

Failure of long-term administration of zopiclone and zolpidem to induce tolerance in mice

The ability of a challenge dose of the cyclopyrrolone zopiclone to antagonize both the convulsions and the increase in t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to the γ-aminobutyric acid type A (GABAA) receptor elicited by isoniazid, an inhibitor of central GABAergic function, was evaluated in mice subjected to long-term treatment (20 mg/kg, i.p.; three times daily for 30 days) with the drug. The effects of zopiclone were compared with those of the imidazopyridine zolpidem and the benzodiazepine flunitrazepam. The challenge dose of zopiclone (10 and 100 mg/kg, i.p., respectively), administered 36 h after the last injection of the chronic treatment protocol, reduced both isoniazid-induced convulsions and the isoniazid-induced increase in [35S]TBPS binding to the same marked extent as in control mice. Similar results were obtained in mice chronically exposed to zolpidem (15 mg/kg), i.p., whereas mice subjected to long-term treatment with flunitrazepam (1 mg/kg, i.p.) became tolerant to this drug. These results indicate that long-term treatment with zopiclone or zolpidem failed to induce tolerance to the effects of these drugs on GABAA receptor function. Consistent with these observations, [35S]TBPS binding was increased (+18 to 28%) 12 and 48 h after, and decreased (-15%) 96 h after, discontinuation of long-term flunitrazepam administration. In contrast, discontinuation of chronic treatment with zopiclone or zolpidem failed to modify this parameter. These data indicate that long-term treatment with the hypnotic zopiclone did not induce discontinuation syndrome in mice.

P-8-5 - Effects of zopiclone, zolpidem and flunitrazepam on nocturnal psychomotor and cognitive functions in normal young subjects

1987) was completed daily each morning. Sleep lab studies were carried out on 7 nights (pre-drug placebo nights 6, 7; drug nights I, 27, 28; post-drug placebo nights 1,7) and included polysomnography, evaluation of subjective sleep quality, subjective and objective awakening quality measured by psychometry. An activity monitor was worn by the patients throughout the 6 weeks to investigate the sleep-wake cycle. Preliminary evaluations demonstrated significant improvement of the anxiety syndrome and the sleep quality during both active compounds, as compared with placebo, with a worsening of symptoms on the I st night of placebo substitution, levelling off until the 7th night. Differential drug effects will be discussed.

Pharmacokinetic-pharmacodynamic modelling of zopiclone effects on human central nervous system.

The present data shows the pharmacokinetics and concentration-effect relationship of a single 7.5 mg oral dose of zopiclone in ten healthy volunteers. Plasma concentrations and effects of zopiclone on central nervous system as quantified by changes in saccadic peak velocity and digit symbol substitution test were measured for 17 hr after ingestion of zopiclone. Pharmacokinetics was described with a linear one-compartment open model. Maximum effects preceded peak plasma zopiclone concentrations causing a clockwise hysteresis, i.e. proteresis, in concentration versus effect loops. Therefore, pharmacodynamics was described both with a tolerance model and a model with distributional pseudo-tolerance where the concentration in the blood sampling site is assumed to equilibrate slower with arterial blood than the site of action of zopiclone. Both models related the changes in pharmacodynamics linearly to changes in zopiclone concentrations. The median (range) values for clearance, volume of distribution and elimination half-life were 21 (15-53) L/hr, 132 (58-161) L and 3.4 (1.7-5.7) hr, respectively. Both pharmacodynamic models were able to describe the relationship between zopiclone concentrations and changes in psychomotor performance equally well. However, because the pharmacodynamics of zopiclone were studied in a non-steady-state situation, the mechanism for proteresis, i.e. true tolerance versus distributional pseudotolerance cannot be identified.

Effects of zopiclone on quality of life in insomnia

All of the components of quality of life can be altered in insomniacs because of sleep disorders themselves but theoretically also in consequence to side effects from hypnotic agents. The presented international study, carried out with a multicentre, randomised and double-blind design, investigated zopiclone effects on quality of life in insomniac patients as compared to placebo. A total of 458 patients completed the study, 231 receiving zopiclone 7.5 mg and 227 receiving placebo, with mean treatment durations of 48 and 44 days. Sleep parameters and quality of life, measured with extensive and validated scales, were assessed at baseline and at 14, 28 and 56 days after admission. Zopiclone showed hypnotic efficacy and significantly greater improvement of quality of life as compared to placebo, both at 14 days and at endpoint.

Effects of zopiclone on sleep and symptoms in schizophrenia: Comparison with benzodiazepine hypnotics

1. Sleep variables and psychiatric symptoms were investigated in 6 male chronic schizophrenic outpatients. 2. The patients were being treated with benzodiazepine(BZD) hypnotics for more than 8 weeks, and BZDs were replaced with zopiclone (ZPC) 15 mg/day. 3. Polysomnographic examinations, subjective sleep assessments and BPRS scoring were performed during BZD therapy and at the end of 8 weeks of ZPC therapy. 4. The doses of neuroleptics and anticholinergic agents remained fixed throughout the study. 5. The amount of slow-wave sleep (SWS) was markedly small and that of stage 1 sleep was moderately large during BZD therapy. 6. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. 7. There were no significant change in the amount of SWS between the treatment. 8. Half of the patients exhibited a sleep-onset REM period (SOREMP) during ZPC therapy. 9. Both total BPRS score and negative symptom score were lower during treatment with ZPC than BZDs. 10. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZD hypnotics and that reduced SWS and SOREMP may be partly involved in the pathophysiology of schizophrenia.

Effects of zopiclone, flunitrazepam, triazolam and levomepromazine on the transient change in sleep-wake schedule: Polygraphic study, and the evaluation of sleep and daytime condition

Osamu Kanno, Hirofumi Watanabe and Hajime Kazamatsuri: Effects of Zopiclone, Flunitrazepam, Triazolam and Levomepromazine on the Transient Change in Sleep-Wake Schedule. Polygraphic study, and the evaluation of sleep and daytime condition. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17 : (2) 229–239. 1. 1. The effects of zopiclone lOmg (ZP), flunitrazepam 1mg (FN), triazolam 0.25mg (TZ) and levomepromazine 5mg (LP) on two models of sleep-wake schedule change-6 hours advanced shift: (A-shift), and 6 hours delayed: (D-shift) — were investigated in 6 healthy volunteers using polysomnography. 2. 2. In A-shift with placebo, TST, SEI, %SR and REM/NREM decreased. ZP, FN and TZ shortened SL. All drugs increased TST and SEI. TZ and LP increased %SR and REM/NREM. 3. 3. In D-shift with placebo, TST decreased, SWSL was prolonged, %S3+4 decreased, and %SR and REM/NREM increased. All drugs increased TST. ZP and LP shortened SWSL. All drugs increased %SWS. ZP, FN and TZ decreased %SR. ZP and FN decreased REM/NREM. 4. 4. Daytime mental and physical conditions were worse than usual on more than half of the days in A- and D-shift. LP and FN caused some inadequate conditions on the following days. Significantly higher REM/NREM was observed in the nights before the days with worse mental conditions in D-shift, and lower REM/NREM in the nights before the days with worse physical conditions in A-shift. 5. 5. It is concluded that TZ and ZP are superior to the others for A-shift and D-shift, respectively.

Effects of zopiclone on subjective evaluation of sleep and daytime alertness and on psychomotor and physical performance tests in athletes

1. In a double-blind cross-over study 8 athletes received during 2 sessions of 2 nights zopiclone (7.5 mg) or placebo. 2. Residual effects on subsequent daytime functions were evaluated both subjectively by visual analogue scales as well as objectively by a test battery measuring psychomotor and physical skills. 3. Zopiclone had some favourable effects on self-estimated sleep quality and daytime sleepiness. 4. Psychomotor and physical performance tests did not show any significant difference between zopiclone and placebo. 5. We conclude that zopiclone has useful hypnotic activity without significant adverse effects on athlethic performance.

Performance and mood following partial sleep deprivation: A randomized, double‐blind crossover study of zopiclone, triazolam, flunitrazepam, ethanol and placebo

AbstractThe effects of zopiclone 7.5 and 15 mg, triazolam 0.25 and 0.5 mg, flunitrazepam 1 and 2 mg, ethanol and placebo on performance, mood and sleep onset latency after partial sleep deprivation, were compared in a randomized, double‐blind, crossover, single‐dose study. Sixteen healthy volunteers of both sexes, aged 21–31 years, were included in the study. The overall assessment of the total psychological measurement indicated that zopiclone 7.5 mg, triazolam 0.25 mg and ethanol (Cmax = 0.40 parts per thousand) did not affect the daytime performance of an unacceptable degree even when given late at light. The findings for flunitrazepam 1 mg were not so uniform, but also seemed acceptable. Zopiclone 15 mg, triazolam 0.5 mg and flunitrazepam 2 mg were rated as not acceptable alternatives. No significant differences were shown concerning mood. The overall assessment for sleep onset latency and subjective alertness indicated that zopiclone 7.5 mg and triazolam 0.25 mg had a more appropriate profile than the other drugs and doses tested.

Modification of GABA turnover in the striatum and hippocampus of the rat after zopiclone.

The effects of zopiclone, a non-benzodiazepine compound that interacts with benzodiazepine receptors, on GABA turnover rate and GABA content in the rat striatum and hippocampus have been studied. Intraperitoneal administration of zopiclone reduced the GABA turnover rates in both the striatum and hippocampus, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA). The effect of zopiclone on AOAA-induced accumulation of GABA in the hippocampus and striatum was blocked by the intraperitoneal injection of the benzodiazepine receptor antagonist Ro 15-3505. Furthermore, zopiclone slightly but significantly decreased GABA content in the hippocampus, the decrease being blocked by coadministration of the benzodiazepine receptor antagonist Ro 15-1788. Our results confirm that the GABAergic system plays a role in the mechanism of action of zopiclone.

Residual Effects of Zopiclone (Imovane)

A double-blind, randomized, cross-over study has been conducted with zopiclone (Imovane), a new cyclopyrrolone hypnotic in ten healthy volunteers. Hypnotic efficacy has previously been demonstrated at a dose of 7.5 mg. The present study was designed to determine the overnight residual effects of different doses of the drug ranging from 2.5 to 10 mg. Measurement of complex reaction time was used as an objective test of impairment of psychomotor function. To supplement this, the volunteers were asked to report, by means of visual analogue scales, any perceived changes in their performance in the complex reaction time test, in their mood, and in the onset and quality of sleep. Complex reaction time testing revealed no significant impairment except at 12 h after the 10 mg dose. Subjective assessments of onset of sleep showed a dose-dependent shortening of sleep latency, confirming the hypnotic action of the drug. Volunteers were aware of a decline in psychomotor performance, of some sleepiness on awakening, and decreased alertness after previous night doses of 7.5 and 10 mg. It is concluded that a dose of 7.5 mg is optimal, producing significant hypnotic effect with minimal residual impairment.

Behavioral Pharmacology of Zopiclone

The pharmacological properties of zopiclone, a cyclopyrrolone derivative, have been studied in comparison with diazepam, nitrazepam, and flurazepam, on behavioral tests in mice and rats, including open-field activity, Skinner box conflict test, hyperemotionality and muricidal behavior of olfactory bulbectomized or raphectomized rats, pentetrazol or electroshock convulsions, inclined screen, rotarod, and thiopental-, ether-, or ethanol-induced anesthesia. Zopiclone exhibited pharmacological properties qualitatively similar to those of benzodiazepines especially in conflict, aggressivity, and pentetrazol-induced convulsion tests. On the other hand, its myorelaxant activity was somewhat weaker than that of the reference drugs. The pharmacological effects of zopiclone were of short duration.

Effects of zopiclone and benzodiazepines on spinal reflexes, anemic decerebrate rigidity and benzodiazepine binding.

Whether or not zopiclone, a new sleep-inducing drug, exerted a similar effect to that of benzodiazepines was examined. The drug inhibited crossed extensor reflexes in chicks and augmented the dorsal root-dorsal root reflexes in rats without affecting the mono- and polysynaptic reflexes. The site of its action was considered to be located in the spinal cord since the effect on the dorsal root reflex was observed also in the spinal rats. Zopiclone selectively reduced the phasic responses of anemic decerebrate rigidity like benzodiazepines in rats. Despite the structural difference from the benzodiazepines, zopiclone dose-dependently inhibited [3H]flunitrazepam binding in rat brain membranes, although the potency was weaker. These results suggested that zopiclone exerts CNS actions via benzodiazepine receptors.

Analysis of site of action of zopiclone on the central respiratory and cardiovascular control mechanisms.

Experiments were performed in vagotomized and paralyzed rabbits with severed carotid sinus nerves and maintained by artificial ventilation under monitoring O2 and CO2 levels in expired air. The phrenic nerve, renal sympathetic nerve activity and EEG were recorded simultaneously with arterial blood pressure and ECG. Effects of zopiclone were compared before and after brain stem transection at the mid-pontine level. Although the period of respiratory burst activity in the phrenic nerve was prolonged (before, 1.7±0.5 sec; after, 21.4±13.7 sec) after mid-pontine transection, the respiratory rhythmic activity was preserved with a slightly change in CO2 levels in expired air (before, 3.55±0.40%; after, 3.35±0.30%). After mid-pontine transection zopiclone (1-10 mg/kg i.v.) prolonged the period of the phrenic respiratory volley (28.3±13.0 sec, p<0.05, N =10) and reduced the total power of both the phrenic (27.8% of the control) and the renal nerve activities (41.0%) significantly. Zopiclone caused a significant decrease in mean blood pressure (27.2% of the control) and heart rate (2.6%). Furthermore the inhibitory action of zopiclone on CO2 response as measured by the total power of the phrenic nerve activity was also observed after the transection. The direction of these changes induced by zopiclone aftei mid-pontine transection was qualitatively the same as that before (Jpn. J. Pharmacol., 32(Suppl.), 66p). These results indicate that zopiclone exerts the respiratory and cardiovascular inhibitory action by acting on the part of the central respiratory and cardiovascular control mechanisms located caudal to mid-pontine level.

Prediction of clinical efficacy of zopiclone by utilizing two psychophysiological tools in healthy volunteers.

The clinical effects of zopiclone were predicted by using two psychophysiological tests: the averaged photopalpebral reflex and the frontal midline theta activity. Zopiclone at 5 and 10 mg showed a rapid, dose-dependent, moderately lasting prolongation of the latencies of the averaged photopalpebral reflex related to the lowering of the arousal level. Diazepam 5 mg increased markedly the frontal midline theta activity, the appearance of which seems to be related to the relief from anxiety, while zopiclone 10 mg only slightly modified the frontal midline theta activity. The results suggest that zopiclone possesses a potent hypnotic effect, whereas its anxiolytic potential in humans is probably low.

O-67 - Effects of zopiclone on the central neural mechanisms of the respiratory and cardiovascular control systems

O-67 - Effects of zopiclone on the central neural mechanisms of the respiratory and cardiovascular control systems