Pharmacological and clinical studies of cyclopyrrolones: zopiclone and suriclone

Among the non-benzodiazepine compounds which have been found to interact with the "GABA receptor-BZ receptor-chloride channel complex," the very chemically original cyclopyrrolone family has a special place. This has been demonstrated using selected pharmacological, biochemical and clinical data obtained with two cyclopyrrolones, zopiclone and suriclone, which, in addition to their capacity of displacing BZ from their sites, simultaneously possess the main pharmacological properties of BZ and well established therapeutic activities, as hypnotic and anxiolytic, respectively. However, although cyclopyrrolones recognize BZ receptor sites, their mechanism of action might not exactly fit with that of BZ. Indeed, using tritiated zopiclone and suriclone, it has been shown that they could act on sites distinct from those of BZ or could induce receptor conformational changes different from those induced by BZ.     

A comparison of zopiclone and propiomazine as hypnotics in outpatients: A multicentre,double-blind,randomized, parallel-group comparison of zopiclone and propiomazine in insomniacs

Summary

In a double-blind, parallel-group study of 135 patients with a mean age of 60 years, zopiclone 5?mg was compared with propiomazine 25?mg. The patients rated their sleep in a diary. There were statistically significant differences in favour of zopiclone for nine out of 13 variables measuring subjective sleep quality and quantity. Concerning side-effects, bad taste was reported more frequently in the zopiclone group and restless legs in the propiomazine group.     

佐匹克隆治疗老年失眠症患者的临床研究

目的:探讨采用佐匹克隆治疗老年失眠症的临床效果及安全性。方法:选取90例老年失眠症患者,随机将其分成研究组和对照组各45例。对照组患者每晚睡前服用1mg艾司唑仑,而研究组患者则在每晚睡前服用7.5 mg佐匹克隆,共服用2周,利用睡眠障碍量表(SDRS)和药物不良反应量表(TESS)对两组患者的治疗效果及不良反应进行分析比较。结果:研究组患者治疗总有效率为95.6%,显著高于对照组77.8%的治疗总有效率,差异具有统计学意义(P<0.05);研究组患者治疗后SDRS评分较治疗前和对照组治疗后均明显缩短,数据差异具有统计学意义(P<0.05);研究组患者不良反应发生率明显低于对照组(P<0.01)。结论:在老年失眠症患者中采用佐匹克隆治疗方案具有更显著的疗效,安全性更高,不良反应少,值得临床推广及应用。     

女珍颗粒联合佐匹克隆治疗更年期失眠症的临床研究

目的 探讨女珍颗粒联合佐匹克隆片治疗更年期失眠症的临床疗效。方法 选取2016年3月—2018年10月在内蒙古自治区精神卫生中心进行治疗的82例更年期失眠患者为研究对象,根据用药的差别分为观察组（41例）和对照组（41例）。对照组给予佐匹克隆片,7.5 mg/次,1次/d,睡前服用;观察组在对照组基础上口服女珍颗粒,6 g/次,3次/d。两组均治疗4周后进行效果对比。结果 经治疗,对照组有效率为82.92%,显著低于治疗组95.12%（P<0.05）。经治疗,两组患者匹兹堡睡眠质量指数量表（PSQI）评分降低;多导睡眠监测（PSG）中入睡时间、觉醒时间降低,总睡眠时间增加,睡眠效率提高;睡眠结构中I期时间缩短,II、III期及快速动眼期时间延长（P<0.05）,且观察组睡眠情况显著优于对照组（P<0.05）。经治疗,两组患者血清中神经递质去甲肾上腺素（NE）、5-羟色胺（5-HT）、多巴胺（DA）水平显著升高（P<0.05）,且观察组神经递质水平显著高于对照组（P<0.05）。经治疗,两组焦虑自评量表评分（SAS）、抑郁自评量表评分（SDS）、SCL-90、Hamilton抑郁量表（HAMD）评分均显著降低（P<0.05）,且观察组上述评分显著低于对照组（P<0.05）。结论 女珍颗粒联合佐匹克隆片治疗更年期失眠症效果良好,可有效减轻失眠症状,改善患者负面情绪,提高患者生活质量,有着良好临床应用价值。     

The acute cognitive effects of zopiclone,zolpidem, zaleplon,and eszopiclone: A systematic review and meta-analysis

The “z-drugs” zopiclone, zolpidem, eszopiclone, and zaleplon were introduced in the 1980s for the treatment of insomnia, as it was observed that the side effect profile associated with these medications were more benign than those related to the benzodiazepines. This meta-analysis set out to ascertain which domains of cognitive function, if any, were affected by the ingestion of these medications. A total of 20 studies met the study inclusion criteria. Results revealed medium effect sizes for zopiclone and zolpidem on measures of verbal memory. An additional medium effect size was observed for zolpidem on attention. Finally, smaller effect sizes were observed for zolpidem speed of processing and for zopiclone on working memory. It is clear from these data that the use of a single dose of the z-drugs in healthy adults as measured in the morning following the exposure does produce a specific rather than a generalized negative effect on cognitive function. However, there were only enough studies to evaluate the individual cognitive effects of the zolpidem and zopiclone medications; the specific effects of zaleplon and eszopiclone cannot be ascertained because only one study met the inclusion and exclusion criteria for the review.     

小剂量阿立哌唑合并佐匹克隆治疗失眠症对照研究

目的探讨小剂量阿立哌唑并佐匹克隆对失眠症的治疗效果和安全性。方法将本院门诊失眠症患者102例随机分成治疗组与对照组,治疗组予以小剂量阿立哌唑并佐匹克隆片口服,每晚1次;对照组予以佐匹克隆片口服,每晚1次。疗程2周。采用睡眠障碍评定量表（SDRS）评定疗效,药物不良反应量表（TESS）评定不良反应。结果治疗第1周末、第2周末,两组SDRS评分均较治疗前显著下降,差异有高度统计学意义（P〈0.01）,且治疗组治疗后的SDRS评分显著低于对照组（P〈0.05）。两组临床疗效比较,差异有统计学意义（P〈0.05）,而TESS评分比较,差异无统计学意义（P〉0.05）,无新增不良反应。结论联合小剂量阿立哌唑治疗失眠症能提高疗效,且不增加不良反应。     

The effects of substituting zopiclone in withdrawal from chronic use of benzodiazepine hypnotics

Twenty-four volunteers (19 women and five men) with insomnia and a history of chronic use of benzodiazepine hypnotics participated in a randomized, double blind, controlled clinical trial. The study was designed to assess the effects of substituting zopiclone (ZOP) – as an hypnotic – among chronic users of flunitrazepam (FLU), and to compare the subsequent withdrawal of ZOP with placebo controlled withdrawal of FLU. During the 5 weeks of a withdrawal protocol, sleep and physiological parameters were assessed by polysomnographic measures for 11 nights and by nightly actigraphic recordings for weeks 1, 3, and 5. Subjective effects of the withdrawal process were evaluated with daily sleep diaries, and with various weekly self-report symptom checklists. Paired t-tests performed on differences in objective sleep parameters between baseline and the last weeks of the withdrawal program showed a significant decrease in sleep quality within the FLU group, but not in the ZOP group. Subjective sleep diaries consistently reflected the objectively measured changes in sleep throughout the withdrawal program, indicating significant changes in sleep parameters only in the FLU group. The results obtained from the self report inventories aimed at assessing withdrawal symptoms, however, revealed no differences between the baseline week and the termination week of the program in any of the groups. After completing the pharmacological withdrawal, all subjects received a short-term cognitive behavioral intervention focused on improving their coping strategies with symptoms of insomnia; they were evaluated immediately after concluding the intervention, and at 3 and 12 month follow-ups. Received: 19 December 1997/Final version: 11 May 1998     

Zopiclone,sleep and health-related quality of life

458 insomniac patients participated in a multinational, randomised, double blind, parallel groups study of zopiclone 7.5 mg versus placebo. Patients received the drug or placebo nightly for 14 days and for a further six weeks on demand. Sleep characteristics and Quality of Life measures were assessed at 14, 28 and 56 days after admission. Both groups of patients improved on these measures, but the active treatment showed significantly greater improvement compared to placebo, both after 14 days and at the end of the trial.     

催眠药扎来普隆、三唑仑、唑吡坦和佐匹克隆对认知操作能力影响的比较

目的 比较催眠药扎来普隆、三唑仑、唑吡坦和佐匹克隆对正常人认知操作能力的影响.方法 8名健康青年男性志愿者,在5次试验（每次间隔1周）中交叉服用扎来普隆10 mg、三唑仑0.25 mg、唑吡坦10 mg、佐匹克隆7.5 mg和安慰剂,采用随机双盲设计给药,分别在服药前4 h、服药后1、2、3、4、6、8、10 h各完成1次认知能力测试,同时观察药物不良反应.测试内容包括：①单双重任务能力（包括计算机控制的4数连加、心理运动能力及二者复合的双重任务）;②光刺激反应时及运动时;③临界闪光融合频率.用重复测量的方差分析比较不同药物和用药后不同时间认知能力的差别.结果 与安慰剂相比,扎来普隆对各项指标无明显不良影响;三唑仑使心理运动能力和临界闪光融合频率下降;唑吡坦和佐匹克隆明显降低心理运动能力、双重任务保持率和临界闪光融合频率.此外,佐匹克隆还显著降低双重任务正确率.用药后约6 h各组的认知能力恢复正常.结论 基于认知操作能力的影响评价,扎来普隆是4种短效催眠药中最安全的药物.