Different sensitivity to ethanol in alcohol-preferring sP and -nonpreferring sNP rats

BACKGROUND AND OBJECTIVES: Clinical research has proposed that initial sensitivity to ethanol may be negatively correlated with levels of subsequent ethanol intake; consistently, alcohol-preferring P rats were found to be less sensitive to the ataxic and sedative/hypnotic effects of ethanol than -nonpreferring NP rats. The present study investigated the initial sensitivity to the ataxic and sedative/hypnotic effects of ethanol and to the sedative/hypnotic effects of pentobarbital and diazepam in selectively bred Sardinian alcohol-preferring sP and -nonpreferring sNP rats. METHODS: In experiment 1, time to lose (onset) and regain (sleep time) the righting reflex after the acute intraperitoneal (ip) administration of 3.0 and 3.5 g/kg ethanol were measured in sP and sNP rats. In experiment 2, sP and sNP rats were required to perform a motor coordination task on a Rota-Rod after the acute intragastric administration of 2.0, 2.5, and 3.0 g/kg ethanol. Experiment 3 assessed onset and sleep time in sP and sNP rats after the acute injection of pentobarbital (40 mg/kg; ip) and diazepam (15 and 20 mg/kg; ip). RESULTS: In experiment 1, sP rats took shorter times to lose the righting reflex and regained this reflex over longer periods of time and at lower blood ethanol levels than sNP rats. In experiment 2, ethanol affected motor coordination to a greater extent in sP than sNP rats. In contrast, results from experiment 3 showed that sP and sNP rats were not differentially sensitive to the sedative/hypnotic effects of pentobarbital and diazepam. CONCLUSIONS: The results of experiments 1 and 2 suggest that sP rats possess a genetically determined, greater sensitivity to the motor impairing and sedative/hypnotic effects of ethanol than sNP rats. Although caution should be adopted before hypothesizing any comparison to humans, these results may feature sP rats as an experimental model of those subsets of human alcoholics with initial high sensitivity to ethanol challenges. Finally, the results of experiment 3 suggest a minimal involvement of the benzodiazepine and barbiturate recognition sites in the differential sensitivity to ethanol of sP and sNP rats.     

A triazolam/amphetamine dose–effect interaction study: dissociation of effects on memory versus arousal

Rationale In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms. Objective The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam. Materials and methods Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures. Results Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam’s effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal. Conclusions Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs’ sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.     

2004-2008年我院安神类中成药应用分析

目的：调查我院2004-2008年中药房现有9种安神类中成药的使用情况,为临床合理用药提供参考。方法：采用金额分析法、药物使用频度（DDDs）分析法对安神类中成药的年销售金额、年DDDs和日用药金额进行统计分析。结果：2004-2008年我院安神类中成药的年销售金额、年销售总金额、年DDDs总值呈增长趋势。结论：我院安神类中成药应用基本合理;虽然中成药价格在下降,但整体销售额却在逐年上升,说明中成药在治疗失眠、心悸等病症中将会发挥越来越大的作用。     

酸枣仁不同炮制品及炒酸枣仁中总黄酮与总皂苷的镇静催眠作用比较

目的：研究比较酸枣仁生品和炒品及总黄酮和总皂苷的镇静催眠作用。方法：采用小鼠活动记数法和协同阈下剂量戊巴比妥钠镇静催眠法。结果：酸枣仁生品以20g／kg剂量及酸枣仁炒品以10g／kg剂量灌胃给药，可显著减少小鼠自发活动次数；酸枣仁生品和炒品以10g／kg和20g／kg剂量灌胃给药均可协同阈下剂量戊巴比妥钠使入睡小鼠数目显著增多。总皂苷以240mg／kg和480mg／kg剂量给药可显著减少小鼠自发活动次数，以480mg／kg剂量给药可显著增加阈下剂量戊巴比妥钠所致翻正反射消失小鼠数；总黄酮以300mg／kg剂量给药可显著减少小鼠自发活动次数、增加阈下剂量戊巴比妥钠所致翻正反射消失小鼠数。结论：酸枣仁生品和炒品均有抑制小鼠自发活动及协同戊巴比妥钠镇静催眠作用，且炒酸枣仁中总黄酮和总皂苷均有抑制小鼠自发活动和协同戊巴比妥钠镇静催眠作用。     

寐安宁口服液镇静催眠作用的实验研究

观察鼠寐安宁口服液对小鼠的镇静催眠作用。结果表明 ,寐安宁口服液 5 0、2 .5 g/kg可明显减少小鼠自主活动次数 ,提高阈下剂量戊巴比妥钠致小鼠的入睡率 ,在本试验所用剂量范围内 ,寐安宁口服液对小鼠具有明显的镇静催眠作用。     

Alcohol and false recognition: a dose-effect study

RATIONALE: The pattern of acute memory impairment produced by alcohol is similar to that produced by the benzodiazepines. However, in contrast to demonstrations that benzodiazepines decrease false recognition rates, results of a recent study suggest that a low dose of alcohol increases false recognition rates; false recognition refers to the phenomenon of mistakenly claiming that one has been exposed previously to a novel item. OBJECTIVE: This study was designed to examine the acute dose-effects of alcohol on false recognition. METHODS: Effects of alcohol (0.27 and 0.60 g/kg) on performance in the Deese/Roediger-McDermott false recognition paradigm were examined in a repeated measures placebo-controlled double-blind design in 18 healthy volunteers. RESULTS: The 0.60 g/kg dose of alcohol significantly reduced true recognition rates (measured by hit rate) and induced a more conservative response bias (measured by C) relative to placebo; however, neither alcohol dose significantly impaired participants' sensitivity in discriminating between old and new words (d'). Neither alcohol dose affected false recognition rates. CONCLUSIONS: Effects of alcohol on false recognition and on response bias may differ from those observed previously with benzodiazepines. A direct comparison at equivalent doses will be necessary to draw conclusions about qualitative differences between alcohol and benzodiazepines.     

催眠药替马西泮的合成

以４－氧化物１为原料，经甲基化、酰化和水解三步反应合成了替马西泮。并分离鉴定了替马西泮产品中的杂质５。     

不同品种的升麻蜜制前后药理活性的比较

目的:比较不同品种升麻蜜制前后镇痛和镇静活性的差异。方法:采用小鼠福尔马林致痛反应、热板法、醋酸扭体实验和小鼠自发活动及举双肢法观察升麻和兴安升麻生药和蜜制品的镇痛和镇静活性。结果:升麻和兴安升麻蜜制品的镇痛和镇静活性均明显强于各自的生药。结论:不同品种升麻其镇痛和镇静活性经过蜜制后显著增强。     

Stimulative and sedative effects of essential oils upon inhalation in mice

This study investigated the stimulative or sedative effects of inhaling fragrant essential oils (EOs) by using a forced swimming test (FST) with mice. This behavioral test is commonly used to measure the effects of antidepressant drugs. The inhalation by mice of EOs, such as ginger oil (p<0.05), thyme oil (p<0.05), peppermint oil (p<0.05), and cypress oil (p<0.01) resulted in 5% to 22% reduction of immobility. The same results were achieved when over-agitation was artificially induced in the mice by an intraperitoneal injection of caffeine (a psycho-stimulant). In contrast, inhalation of some EOs by the mice resulted in increased immobility. To evaluate more correctly the sedative effects of EOs, the immobility of over-agitated mice induced with caffeine was ascertained after the inhalation of various EOs. Inhalation of lavender oil (p<0.01) and hyssop oil (p<0.01) increased the immobile state in mice that were treated with caffeine. The results of this study indicate that the inhalation of essential oils may induce stimulative or sedative effects in mice.     

Prostaglandin synthetase inhibitors antagonize the depressant effects of ethanol

Several studies indicate that ethanol may depress the central nervous system by altering neurotransmitter release. Evidence obtained from the peripheral nervous system suggests that prostaglandins act as negative feedback inhibitors of transmitter release. If a similar process occurs in the brain, then perhaps ethanol affects transmitter release via a mechanism involving prostaglandins. Prostaglandin synthetase inhibitors were administered to adult HS/Ibg male mice prior to intraperitoneal injection of a hypnotic dose of either ethanol, propanol, or t-butanol. A significant decrease in the length of alcohol sleep time was found: in the ethanol study, this was coupled with a significant increase in waking blood alcohol levels. These rresults indicate that inhibition of prostaglandin synthesis alters CNS sensitivity to the depressant effects of alcohol. When the same inhibitors were administered prior to other sedative hypnotics, i.e., pentobarbital and chloral hydrate, no effect was found. This suggests that prostaglandins may be specifically involved in the biochemical mechanism of alcohol depression.