缬草挥发油与水提物镇静催眠作用比较研究

摘 要 目的: 了解缬草镇静催眠的主要药效物质,为深入研究其有效成分提供物质基础。方法: 通过缬草挥发油急性毒性实验,了解挥发油毒性的大小,确定药效实验剂量。采用镇静催眠的药效学实验,比较缬草挥发油与水提物协同戊巴比妥钠对小鼠的催眠作用。结果:小鼠灌胃缬草挥发油的LD₅₀为278.99 g·kg^-1(以生药计),从而确定药效试验的给药剂量为高剂量组(85.71 g·kg^-1)、中剂量组(57.14 g·kg^-1)和低剂量组(28.57 g·kg^-1);缬草镇静催眠药效学实验表明,缬草挥发油可促进小鼠入睡效率,延长小鼠睡眠时间;水提物仅可延长小鼠的睡眠时间,与水提物相比,缬草挥发油能有效延长小鼠的睡眠时间。结论:缬草挥发油的镇静催眠效果明显优于其水溶性物质。     

安睡片镇静催眠作用研究

目的研究安睡片的镇静催眠作用。方法安睡片高剂量（1200mg·kg^-1）、中剂量（900mg·kg^-1）、低剂量（600mg·kg^-1）给小鼠连续灌胃30天,观察安睡片对阈下剂量戊巴比妥钠催眠试验、阈剂量戊巴比妥钠催眠试验、巴比妥钠睡眠潜伏期试验的影响。结果安睡片高剂量能够提高小鼠睡眠发生率（58．33％）;高、中剂量能显著够延长小鼠睡眠时间;高、低剂量能显著缩短小鼠的睡眠潜伏期。     

民康胶囊对小鼠睡眠功能影响实验研究

目的研究民康胶囊对小鼠睡眠功能的影响。方法给予小鼠连续灌胃给药30天后,分别进行直接睡眠实验、延长戊巴比妥钠睡眠时间实验、戊巴比妥钠阀下剂量催眠实验、巴比妥钠睡眠潜伏期实验。结果民康胶囊对小鼠无直接睡眠作用（P〉0．05）;0．81g·kg^-1。剂量组能明显延长戊巴比妥钠对小鼠的睡眠时间（P〈0．05）、增加戊巴比妥钠阁下催眠剂量入睡动物数（P〈0．05）．结论民康胶囊具有改善睡眠功效。     

绒毛钩藤影响中枢神经系统的药理学研究

目的研究绒毛钩藤对中枢神经系统的药理作用。方法小鼠自主活动实验观察其镇静作用;戊巴比妥钠阁下催眠实验观察其催眠作用;士的宁致小鼠惊厥实验观察其抗惊厥作用。结果自主活动试验中．绒毛钩藤提取物（0．16g·kg^-1）灌胃给药后,小鼠60min时的自主活动计数与生理盐水组相比．明显减少（P〈0．01）。在戊巴比妥钠阁下催眠实验中,绒毛钩藤低（0．16g·kg^-1）,中（0．32g·kg^-1）剂量灌胃给药后,小鼠翻正反射消失的个数与生理盐水组比较。均明显增多（P〈0．01）。士的宁致小鼠惊厥实验中。绒毛钩藤提取物灌胃给药后．与生理盐水组比较,中（0．32g·kg^-1）剂量组小鼠死亡数目明显减少（P〈0．01）,高（0．64g·kg^-1）剂量组小鼠死亡数目明显增多（P〈0．01）。结论绒毛钩藤在低剂量和中剂量对中枢神经系统有抑制作用,在高剂量对中枢神经系统有兴奋作用。     

缬草镇静和抗惊厥药理研究

目的探讨缬草的镇静、催眠和抗惊厥作用药理特性。方法1、利用缬草的水提物对小鼠自发活动的影响以及对戊巴比妥钠致小鼠睡眠的协同作用；2、利用缬草的水提物对戊四唑诱发小鼠惊厥的影响。结果缬草水提物可增加戊巴比妥钠小鼠睡眠时间，能降低小鼠前肢上举次数；对戊四唑诱发小鼠惊厥虽无明显影响，但能明显延长其诱发惊厥的潜伏期。结论缬草的水提物具有显著的镇静和抗惊厥作用。     

缬草镇静和抗惊厥药理研究

目的探讨缬草的镇静、催眠和抗惊厥作用药理特性.方法 1、利用缬草的水提物对小鼠自发活动的影响以及对戊巴比妥钠致小鼠睡眠的协同作用;2、利用缬草的水提物对戊四唑诱发小鼠惊厥的影响.结果缬草水提物可增加戊巴比妥钠小鼠睡眠时间,能降低小鼠前肢上举次数;对戊四唑诱发小鼠惊厥虽无明显影响,但能明显延长其诱发惊厥的潜伏期.结论缬草的水提物具有显著的镇静和抗惊厥作用.     

清风胶囊镇静催眠作用的实验研究

目的：研究清风胶囊的镇静作用。方法：通过小鼠自发活动实验和戊巴比妥钠阈下剂量诱导睡眠及睡眠时间实验,观察清风胶囊的镇静作用。结果：低、中、高三剂量清风胶囊（1．0,2．0,4．0g／kg,ig）能明显减少小鼠的自发活动,抑制由吗啡引起的小鼠兴奋性增加,使戊巴比妥钠阈下睡眠剂量诱导入睡小鼠数增多,并明显延长戊巴比妥钠的睡眠时间。结论：清风胶囊具有一定的镇静催眠作用,并呈现一定的量效关系。     

红景天联合多维元素对小鼠运动性疲劳的影响

目的：观察红景天联合多维元素对小鼠运动性疲劳的影响。方法：似随机抽样法将40只雄性小鼠分为4组,分别为空白对照组、红景天（质量浓度为0．78g·kg^-1）联合多维元素（质量浓度为0．21g·kg^-1）低剂量组、红景天（质量浓度为1．56g·kg^-1）联合多维元素（质量浓度为0．42g·kg^-1）中剂量组、红景天（质量浓度为3．12g·b^-1）联合多维元素（质量浓度为0．84g·kg^-1）高剂量组。对4组雄性小鼠连续灌胃给药7d后,测定小鼠负重游泳时间、血乳酸浓度、肝糖原含量3个指标。结果：红景天联合多维元素能延长小鼠的负重游泳时间、降低血乳酸浓度、提高肝糖原含量。结论：红景天联合多维元素对小鼠具有抗运动性疲劳作用。     

新化合物B2镇静催眠作用机制的初探

本试验选用GABAA受体激动剂蝇蕈醇、非竞争性拮抗剂印防己毒素、竞争性拮抗剂荷包牡丹碱、苯二氮卓拮抗剂氟马西尼、GABA合成关键酶GAD的抑制剂盐酸氨基脲,观察它们对新化合物B2镇静催眠作用的影响。将雄性ICR小鼠分为4组,每组10只,分别为空白对照组、B2组（灌胃给药）、拮抗剂或者激动剂组（腹腔注射给药）、B2与拮抗剂或激动剂联合给药组,各组给予相应药物后均腹腔注射闽上剂量的戊巴比妥钠（39mg·kg^-1）,以翻正反射消失为标志,记录小鼠睡眠时间。本试验所选用的激动剂或拈抗剂的剂量均对阈上剂量戊巴比妥钠诱导的小鼠睡眠情况无明显影响。结果显示,在B2与蝇蕈醇协同试验中,空白对照组小鼠睡眠时间为41．9±2．8min,B2（3．75mg·kg^-1）组小鼠的睡眠时间为49．3±2．3min,而B2与蝇蕈醇（0．1mg·kg^-1）合并给药后,小鼠的睡眠时间延长至64．0±7．3min,与B2组相比,显示出明显的协同作用,提示B2镇静催眠作用可能通过GABA。     

黄秋葵镇静催眠活性部位的筛选研究

目的黄秋葵不同极性提取部位对小鼠镇静催眠活性的研究。方法连续7 d灌胃给予小鼠不同提取部位高、低剂量(240、80 mg·kg-1)的黄秋葵,观察其对小鼠自主活动、阈下剂量戊巴比妥钠所致入睡率、阈上剂量戊巴比妥钠致入睡潜伏期与持续睡眠时间的影响。结果黄秋葵醇总提物及正丁醇层、水层和水提物可以显著抑制小鼠的自主活动,增加阈下剂量所致入睡率,缩短阈上剂量致睡眠潜伏期,延长阈上剂量致睡眠时间。结论黄秋葵醇提物正丁醇层、水层和水提物为镇静催眠活性部位。     

Effects of valerian root oil, borneol, isoborneol, bornyl acetate and isobornyl acetate on the motility of laboratory animals (mice) after inhalation]

The aromatherapeutical use of commercial valerian root oil (Chinese origin) and of pure fragrance compounds--borneol, isoborneol, bornyl acetate (main constituent of the proved valerian root oil) and isobornyl acetate--as potentially drugs with sedative effects after inhalation was investigated in an animal experiment (mice). In additional analyses the mice were treated i.p. by caffeine and distinct sedative effects were observed only by inhalation of the cited substances.     

Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs and Valeriana edulis hydroalcoholic extract in mice

It has been declared frequently that valerian may potentiate the effect of other central nervous system (CNS) depressant drugs, however there has been a lack of experimental data. We have evaluated the profile of the interactions between the ethanol extract of Valeriana edulis spp procera and six CNS depressant drugs using an exploratory model to test the sedative effect in mice. All the compounds tested showed a dose-dependent sedative effect with the following ED50 values: valerian 181.62, diazepam 1.21, ethanol 1938, pentobarbital 11.86, buspirone 1.04, haloperidol 0.41 and diphenhydramine 17.06 mg kg-1. An isobolographic analysis was used to evaluate the sedative interaction of the intraperitoneal co-administration of 1:1 fixed-ratio combination of equi-effective doses of valerian extract with each CNS depressant drug. The ED50 theoretical (Zadd) and experimental (Zexp) for each combination were: valerian+diazepam,Zadd=91.41 mg kg-1, Zexp=81.64 mg kg-1; valerian+ethanol, Zadd=1060.22 mg kg-1, Zexp=687.89 mg kg-1; valerian+pentobarbital, Zadd=96.74 mg kg-1, Zexp=151.83 mg kg-1; valerian+buspirone, Zadd=91.33 mg kg-1, Zexp=112.73 mg kg-1; valerian+haloperidol, Zadd=91.01 mg kg-1, Zexp=91.52 mg kg-1; valerian+diphenhydramine, Zadd=99.34 mg kg-1, Zexp=123.52 mg kg-1. Neither synergistic nor attenuate effects were found in any of the combinations evaluated. We concluded that the valerian extract did not potentiate the sedative effect of commonly prescribed CNS depressant drugs as was expected. The additive effect found through the isobolographic analysis suggested that the sedative effect of V. edulis resulted from the activation of common mechanisms of haloperidol, diazepam, buspirone, pentobarbital, diphenhydramine and ethanol.     

Drug utilization review of sedative/hypnotic agents in Texas Medicaid patients. Texas Medicaid Vendor Drug Program Drug Utilization Review Board

OBJECTIVE: To assess use of sedative/hypnotic agents in Texas Medicaid patients and evaluate practitioner receptiveness to intervention letters concerning sedative/hypnotic prescribing generated by the Texas Medicaid Drug Utilization Review (DUR) Board. DESIGN: Retrospective DUR. SETTING: Texas Medicaid retrospective DUR program. PATIENTS OR OTHER PARTICIPANTS: 244 Texas Medicaid patients and 291 Texas physicians. INTERVENTION: Patient profiles for Texas Medicaid patients were reviewed retrospectively to quantify sedative/hypnotic prescribing practices. Intervention letters were prepared and sent to physicians directly involved in the care of patients receiving excessive sedative/hypnotic therapy. Physician responses were categorized based on information presented in the intervention letter and circumstances surrounding the identified patient. Prescribing practices were assessed approximately 1 year after the intervention to determine the impact of intervention letters on prescribing. MAIN OUTCOME MEASURE: Physician response to intervention letter. RESULTS: Responses were received from 208 of 291 physicians (71.5%). Approximately 40% of physicians agreed in principle with the suggestions offered by the Texas Medicaid DUR Board to minimize chronic sedative/hypnotic use. Almost one-half of these physicians had discontinued sedative/hypnotic therapy for the identified patients 1 year after the intervention. Approximately 9% justified continued sedative/hypnotic use based on patient diagnosis or refractory response to treatment, and 55 physicians (26.4%) were unwilling to alter therapy because of patient-specific factors. CONCLUSION: Through the use of retrospective DUR, Texas Medicaid patients receiving excessive amounts of sedative/hypnotic agents were identified and improvements in sedative/hypnotic therapy were initiated. DUR can be useful not only in identifying problem areas, but also in encouraging physicians to modify prescribing practices through educational means.     

不同比例五味子宁神口服液镇静催眠作用研究

目的:寻找五味子宁神口服液镇静催眠作用的最佳配伍比例。方法:通过对小鼠自发活动的影响、对戊巴比妥钠的协同作用、对中枢神经递质的影响等3方面药理学研究,探讨五味子宁神口服液不同配伍比例的镇静催眠作用。结果:五味子宁神口服液以原方用药25%五味子比例作用最好。结论:五味子宁神口服液组方配伍是合理的。     

Investigation of the effects of peppermint oil and valerian on rat liver and cultured human liver cells

1. The aim of the present study was to investigate the effects of peppermint oil and valerian on rat liver and cultured human hepatoma cells. 2. Rats received a single oral dose of peppermint oil (8.3-830 microL/kg) or valerian (0.31-18.6 g/kg), or daily oral doses of 83 microL/kg peppermint oil or 3.1 g/kg valerian for 28 days. After 24 h, rats were anaesthetized and measurements made of bile flow, liver function and in vivo sinusoidal area. Livers were then removed for histology. 3. Bile flow was unaffected by any treatment, except acute high-dose peppermint oil (830 microL/kg; 70% increase in flow). No change in liver enzyme activity was found, except for a 45% increase in alkaline phosphatase after chronic peppermint oil. No change in sinusoidal area in vivo or in histology was found following any treatment, although pretreatment with carbon tetrachloride reduced sinusoidal bed area and produced histological damage. Incubation of human hepatoma cells with 0.5 microL/mL (but not 0.05 microL/mL) peppermint oil or 20 mg/mL (but not 2 mg/mL) valerian resulted in increased cell death. 4. In conclusion, the present study demonstrated in vitro toxicity of high doses of valerian and peppermint oil in cultured human hepatoma cells and, at doses 2-3 orders of magnitude greater than those recommended for human use, an increase in rat bile flow after acute peppermint oil and an increase in alkaline phosphatase after chronic peppermint oil.     

Telemetry as a tool to measure sedative effects of a valerian root extract and its single constituents in mice

Valeriana officinalis L. is a popular herbal treatment for mild sleep disorders. Clinical and non-clinical studies found contradictory results for valerian extracts and single constituents regarding the influence on sleep parameters. It was the aim of this study to investigate the sedative effects of a valerian root extract. Therefore, locomotor activity and core body temperature were recorded in male mice using radiotelemetry. A 70 % ethanolic extract prepared from the roots of V. officinalis (s. l.) and some of its single constituents, valerenic acid, linarin, and apigenin, were tested for effects on locomotion and body temperature over 180 minutes after oral administration. The extract was tested in a dose range of 250-1000 mg/kg, and only a dose of 1000 mg/kg valerian extract showed a mild short-term sedative effect with reduced locomotor activity between 66-78 min minutes after administration. Paradoxically, an increased activity was observed after 150 minutes after gavage. A dose of 1 mg/kg valerenic acid produced an intermittent stimulation of activity. However, a mild short-term sedative effect was found for linarin at 12 mg/kg and apigenin at 1.5 mg/kg. Considering the cumulative locomotor activity over the observation period of 180 min, it is concluded that neither the extract nor one of the compounds had considerable sedative effects. More precisely, the observed short-term changes in activity pattern indicate that valerian extract as well as the flavonoids linarin and apigenin are rather effective to reduce sleep latency than to act as a sleep-maintaining agent.     

咪达唑仑鼻用凝胶喷雾剂的镇静催眠作用研究

目的：对咪达唑仑鼻用凝胶喷雾剂的镇静催眠作用进行初探。方法：采用镇静、催眠实验,考察味达唑仑通过经鼻腔给药途径对小鼠自发活动和对戊巴比妥钠催眠作用的影响,以及对小鼠抬举双前肢的影响。结果：咪达唑仑鼻用凝胶喷雾剂经鼻腔给药后,可明显降低小鼠的自主活动次数,并具有良好的量效关系;可极显著地使阂下剂量戊巴比妥钠导致小鼠的入睡只数增加;各剂量组均可明显缩短给予戊巴妥钠阈上剂量后小鼠的入睡时间并延长其睡眠时间;可明显减少2min内小鼠的抬举双前肢的次数．结论：味达唑仑鼻用凝胶喷雾剂具有明显的镇静催眠作用．     

益脑康胶囊主要药效学研究

目的：观察益脑康胶囊的镇静、催眠和对东莨菪碱所致小鼠记忆获得障碍的改善作用。方法：以东莨菪碱造成动物记忆获得障碍，采用避暗法测定；另观察益脑康对正常小鼠的自主活动和对戊巴比妥钠催眠剂量的影响。结果：益脑康胶囊对东莨菪碱所致动物的学习记忆障碍有改善作用，并有明显的中枢神经抑制作用。结论：益脑康胶爱有明显的益智、镇静、催眠作用。     

Medicinal plants for insomnia: a review of their pharmacology, efficacy and tolerability

A number of medicinal plants are traditionally endowed with anxiolytic or sedative properties and, in the context of this revue, both indications are considered since the former may induce a mood conducive to the latter. For any sleep-inducing drug to be effective, a tranquil ambience needs to be established a priori. Thus, physical ailments (i.e. pain), factors interfering with sleep (i.e. noise), psychological conditions causing stress, psychiatric illnesses (i.e. depression) and other drugs that interfere with sleep (i.e. caffeine) need to be controlled, if possible. Kava-kava is a well-established hypnotic drug, with a rapid onset of effect, adequate duration of action and minimal morning after-effects. However, reports of serious hepatotoxicity with this preparation have led to it being banned in most countries worldwide. On the other hand, side-effects with valerian would appear to be bland indeed. However, it's slow onset of effect (2-3 weeks) renders it unsuitable for short-term use (i.e. 'jet-lag'), but it does have profound beneficial effects on sleep architecture (augments deep sleep) that may make it particularly suitable for long-term use and for the elderly. In a personal trial (not double-blind) in stress-induced insomnia, both kava and valerian improved sleep and the ill-effects of stress, and the combination of the two was even more effective for the control of insomnia. Aromatherapy (lavender, chamomile, Ylang-Ylang) would appear to improve sleep, but how practical a form of treatment this may be remains to be determined. The only other plant drug that may have some effect on sleep is melissa, but reports are too scanty to form any opinion about this. Based on animal experiments, passion flower (passiflora) may have a sedative action, but the sedative action of hops has not been investigated in any detail. In conclusion, there is a need for longer-term controlled studies with some of these compounds (particularly valerian). Aromatherapy constitutes a tantalising possibility. In the interpretation of this review, it should be borne in mind that the evidence on which it is based is often incomplete or missing, but that is all that is available. Consequently some conjecture on the part of the author is inevitable and should be appreciated as such.     

120例海洛因依赖者使用镇静催眠药物情况分析

目的：了解强制隔离戒毒中心海洛因依赖者使用镇静催眠药物情况。方法：自编镇静催眠药物使用调查表,对2010年在所的海洛因依赖者合并镇静催眠药物的共计120例进行调查。调查项目包括一般情况、药物使用种类、使用原因、使用方法、使用次数和剂量等,并逐一进行分析。结果：海洛因依赖者合并使用镇静催眠药占35．7％,其中发生依赖为39．1％。用于镇静催眠占70．12％;使用种类以氯硝西泮为主,占72．5％;结论：海洛因依赖者因失眠、焦虑等症状确有必要使用镇静催眠药,但是应严格控制适应症与时间,以免造成医源性药物滥用。