酸枣仁汤的镇静催眠作用

目的对酸枣仁汤镇静催眠药理作用进行初探。方法采用镇静催眠实验观察酸枣仁汤对小鼠自主活动的影响 ,协同戊巴比妥钠对小鼠的催眠作用。结果酸枣仁汤能明显减少小鼠自主活动次数 ,增加阈下剂量戊巴比妥钠致小鼠睡眠只数 ,延长阈上剂量戊巴比妥钠致小鼠睡眠时间。结论酸枣仁汤有明显的镇静、催眠作用。     

迎春花水提取物镇静催眠作用的研究

目的：研究迎春花水提取物镇静催眠的影响。方法：取昆明种小鼠30只,随机分为生理盐水组、0.1g/kg、0.2g/kg迎春花水提取物组。采用抖笼法测定小鼠自发活动和对阈上、阈下剂量戊巴比妥钠小鼠睡眠时间的影响。结果：0.1g/kg、0.2g/kg的迎春花水提取物对小鼠自发活动具有明显抑制作用（P〈0.05;P〈0.01）。0.1g/kg、0.2g/kg的迎春花水提取物能显著（P〈0.05;P〈0.01）加速戊巴比妥钠的入睡时间和显著（P〈0.05;P〈0.01）延长戊巴比妥钠的睡眠时间,并与戊巴比妥钠有协同作用。结论：迎春花水提取物具有明显的抑制小鼠自发活动和镇静催眠作用。     

一种拟青霉菌丝体冻干粉对小鼠的镇静催眠作用

目的研究一种拟青霉菌丝体(HPC)冻干粉的镇静催眠作用.方法采用自发活动仪记录法、小鼠走动时间和举双肢法、阈下剂量戊巴比妥钠诱导小鼠睡眠法观察受试药的镇静催眠作用.结果 HPC可抑制小鼠的自发活动;缩短小鼠入睡潜伏期,延长小鼠睡眠持续时间. 结论 HPC具有一定的镇静催眠作用.     

北五味子的镇静、催眠作用

目的对北五味子水提取物镇静、催眠药理作用进行初探。方法采用镇静、催眠实验观察北五味子水提取物对小鼠自主活动的影响 ,协同戊巴比妥钠对小鼠的催眠作用。结果北五味子水提取物能明显减少小鼠自主活动次数 ,增加阈下剂量戊巴比妥钠致小鼠睡眠只数 ,延长阈上剂量戊巴比妥钠致小鼠睡眠时间。结论北五味子水提取物有明显的镇静、催眠作用。     

无糖型宁心安神糖浆对小鼠镇静催眠作用的研究

目的 研究无糖型宁心安神糖浆(SNAS)的镇静、催眠作用.方法 采用自主活动试验、戊巴比妥钠阈上催眠剂量试验、睡眠试验、戊巴比妥钠阈下催眠剂量试验,每个试验均选择ICR小鼠60只,随机分为6组,每组10只,分别为空白对照组,安神补脑液组,蔗糖型宁心安神糖浆组,SNAS高、中、低剂量(100、50、25 mL/kg)组,观察SNAS对小鼠的镇静和催眠作用.结果 SNAS能明显减少小鼠的自主活动次数,增加阈下剂量戊巴比妥钠致小鼠入睡数量,延长小鼠睡眠时间,缩短入睡潜伏期.结论 无糖型宁心安神糖浆具有明显的镇静、催眠作用.     

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．     

Sedative and hypnotic effects of supercritical carbon dioxide fluid extraction from Schisandra chinensis in mice

Schisandra chinensis is a traditional Chinese medicine that has been used for treating insomnia and neurasthenia for centuries. Lignans, which are considered to be the bioactive components, are apt to be extracted by supercritical carbon dioxide. This study was conducted to investigate the sedative and hypnotic activities of the supercritical carbon dioxide fluid extraction of S. chinensis (SFES) in mice and the possible mechanisms. SFES exhibited an obvious sedative effect on shortening the locomotor activity in mice in a dose-dependent (10–200 mg/kg) manner. SFES (50 mg/kg, 100 mg/kg, and 200 mg/kg, intragstrically) showed a strong hypnotic effect in synergy with pentobarbital in mouse sleep, and reversal of insomnia induced by caffeine, p-chlorophenylalanine and flumazenil by decreasing sleep latency, sleep recovery, and increasing sleeping time. In addition, it produced a synergistic effect with 5-hydroxytryptophan (2.5 mg/kg, intraperitoneally). The behavioral pharmacological results suggest that SFES has significant sedative and hypnotic activities, and the mechanisms might be relevant to the serotonergic and γ-aminobutyric acid (GABA)ergic system.     

参芪五味子胶囊镇静、抗应激作用研究

目的:研究参芪五味子胶囊镇静、抗应激的作用。方法:采用戊巴比妥钠阈下剂量及催眠剂量观察参芪五味子胶囊对戊巴比妥钠小鼠催眠的协同作用;采用小鼠游泳、常压下耐缺氧实验观察参芪五味子胶囊对小鼠的抗应激作用。结果:参芪五味子胶囊能显著延长戊巴比妥钠小鼠的睡眠时间,增加阈下剂量戊巴比妥钠入睡小鼠只数;显著延长小鼠游泳时间和耐缺氧时间。结论:参芪五味子胶囊具有镇静、抗应激的作用。     

柏子仁总萜类成分药理活性及提取工艺研究

目的探讨从柏子仁中提取总萜类成分的最佳工艺及总萜类成分的镇静、催眠和耐缺氧作用。方法以均质时间、温度、料液比和次数4个因素进行考察,每个因素3个水平,采用L9(34)正交试验优选提取工艺。观察柏子仁总萜类成分对小鼠自发活动、戊巴比妥钠诱导小鼠睡眠时间和睡眠个数及缺氧小鼠存活时间的影响。结果以甲醇溶液作为提取溶剂,提取温度80℃,料液比1∶10,均质10 min,均质提取1次为最佳提取工艺;总萜类成分能抑制小鼠的自发活动,延长戊巴比妥钠诱导的小鼠睡眠时间,增加小鼠睡眠个数,延长缺氧小鼠的存活时间。结论柏子仁总萜类成分具有镇静、催眠和耐缺氧作用;提取方法应用均质法操作简单、效率高,适用于柏子仁总萜类成分的提取。     

Sedative and anticonvulsant activities of styrax after oral and intranasal administration in mice

Context: Styrax, resin of Liquidambar orientalis Mill. (N.O. Hamamelaceae), belongs to resuscitation-inducing aromatic herbs in traditional Chinese medicine and functions in inducing resuscitation and restoring conscientiousness.

Objective: The possible sedative and anticonvulsant activities of styrax on CNS were investigated. The onsets of action of two different routes (oral and intranasal administration) were compared.

Materials and methods: Styrax was tested for sedative, hypnotic, and anticonvulsant effects using locomotor activity evaluation, pentobarbital-induced sleeping time, and pentylenetetrazol (PTZ)-induced convulsion, respectively.

Results: After oral administration (25, 50, 100?mg/kg), styrax prolonged the sodium pentobarbital-induced sleeping time. In comparison with oral administration, intranasal administration (12.5, 25, 50?mg/kg) prolonged the sleeping time at lower dosage. Moreover, styrax (100 and 200?mg/kg) promoted a significant protection against PTZ-induced seizures and mortality 30?min after oral administration. In contrast, 5?min after intranasal administration, styrax promoted significant protection at lower dosages (25 and 50?mg/kg). These data show that styrax had faster onset of action (5 vs. 30?min) and better anticonvulsant efficacy (25, 50 vs. 100, 200?mg/kg) by intranasal route in comparison with that by intragastric route. Styrax decreased the spontaneous locomotor movements at 100?mg/kg during 5–60?min interval after oral administration.

Discussion and conclusion: Styrax has sedative and anticonvulsant activities. Furthermore, styrax has faster onset of action as well as more potent efficacy after intranasal administration at lower dosage than by intragastric route. This result illustrates that intranasal administration may act as a promising alternative to conventional routes of administration.     

桔梗中远志酸型皂苷的化学研究

目的分离、鉴定桔梗［Platycodon grandiflorum (Jacq.)A.DC］根中的远志酸型皂苷类化学成分。方法 采用乙醇提取、乙酸乙酯萃取，大孔树脂柱色谱、硅胶柱色谱及高效液相色谱等方法进行分离，得到3个化学成分，运用IR，MS，¹H NMR和¹³C NMR等光谱法鉴定化合物的结构。结果分离鉴定了3种三萜皂苷：3-O-β-D-laminaribiosyl polygalacic acid (I)，3-O-β-D-glucopyranosyl polygalacic acid (II)及polygalacin D (III)。结论化合物I是新化合物，II，III为已知化合物。化合物II为首次从该植物中分得，化合物I和II也是首次从桔梗中分离得到的单糖链糖苷。     

Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism

Ganoderma lucidum has been used for the treatment of a variety of diseases. For the first time here we report a detailed study on the mechanisms and effects of G. lucidum aqueous extract (GLE) on sleep and its sedative activity. GLE showed no effects on sleep architecture in normal rats at doses of 80 and 120 mg/kg. However, GLE significantly decreased sleep latency, increased sleeping time, non-REM sleep time and light sleep time in pentobarbital-treated rats. Suppression of locomotor activity in normal mice induced by GLE was also observed. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3.5 mg/kg showed a significant antagonistic effect on the shortening in sleep latency, increase in sleeping time, non-REM sleep time or light sleep time in pentobarbital-treated rat induced by GLE. Significant effect was also observed with GLE on delta activity during non-REM sleep and flumazenil did not block this effect. In conclusion, GLE may be a herb having benzodiazepine-like hypnotic activity at least in part.     

Central nervous system activity of new pyrimidine-8-on[2,1-f]theophylline-9-alkylcarboxylic acids derivatives

The appropriate esters 1-3 were synthesized by the alkylation of unsubstituted pyrimidin-8-on[2,1-f]theophylline I with ethyl-chloroacetate, ethyl-acrylate and ethyl-4-bromobutyrate. The acids 4-6 were obtained by hydrolysis of the esters 1-3, and transformed into Na salts 4a-6a. Amidation of the ester 1 with 25% ammonia and hydroxylamine led to amide 7 and N-hydroxyamide 8. The bromination of 1 gave 7-bromo intermediate 9 transformed to the 7-amino derivatives via nucleophilic substitution with phenylpiperazine for compound 10 and morpholine for compound 11. In the reaction of 9, 10 and 11 with sodium alcoholate, the corresponding Na salts 12a-14a were obtained. The pharmacological properties of the compounds were tested in CNS activity screening. It was found that all of the investigated compounds produced significant sedative effects in behavioral tests except weak activity of pyrimido[2,1-f]theophylline-9-sodium acetate 4a. The potent activity of pyrimido[2,1-f]theophylline-9-sodium butyrate 6a, pyrimido[2,1-f]theophylline-9-acetamide-7,7-N-phenylpiperazine-pyrimido[2,1-f]theophylline-9-sodium acetate 13a, and 7-N-morpholine-pyrimido[2,1-f]theophylline-9-sodium acetate 14a was observed. They inhibited spontaneous locomotor activity, potentiated sedation and prolonged duration of sleeping time after thiopental sodium administration. All compounds had no effects in the test of analgesia and they showed weak anti-convulsant properties. The results of this investigation may suggest hypnotic, sedative and/or tranquillizing properties of the tested compounds.     

Comparative Effects of Medetomidine Enantiomers on in vitro and in vivo Microsomal Drug Metabolism

Abstract: The effects of dexmedetomidine, a selective α₂-adrenoceptor agonist, and its levo enantiomer (MPV-1441), on in vitro microsomal P450-dependent drug-metabolizing activities as well as on in vivo aminopyrine elimination and hexobarbital sleeping time were studied. Both enantiomers inhibited the oxidative metabolism of several model substrates and testosterone in rat liver microsomal incubations. Microsomal activities derived from control animals or rats pretreated with phenobarbital were more sensitive to inhibitory effects of dexmedetomidine than those from rats treated with 3-methylcholanthrene. Enzyme activities in human liver microsomes were also inhibited by dexmedetomidine. Retardation of the elimination of aminopyrine was dose-dependent; elimination was marginally retarded with doses up to 100 μg/kg (from 17 to 23 min.; both enantiomers). Higher doses of the levo enantiomer prolonged aminopyrine half-life to 78 (1 mg/kg) and 162 min. (10 mg/kg). The hexobarbital sleeping time was prolonged by the dose of 1 mg/kg of the levo enantiomer (128 min. versus 20 min. in controls), while the dose of 0.1 mg/kg had no effect (23 versus 20 min.). These studies indicate that both enantiomers of medetomidine are inhibitors of microsomal drug metabolism in vitro, but significant effects on aminopyrine elimination or hexobarbital sleeping time are apparent only at doses, which do not allow the use of dexmedetomidine because of excessive sedative effect.     

Sedative potency and 2-[125I]iodomelatonin binding affinity of melatonin analogues

Melatonin (5-methoxyN-acetyltryptamine), the hormone synthesized and released from the pineal gland each night, has sedative and sleep-promoting effects in experimental animals and man. In the present study, the sedative effect of melatonin and a number of analogues was determined by examining their ability to extend the duration of the loss of righting reflex (sleeping time) in mice injected with pentobarbitone (50 mg/kg IV). All of the analogues tested produced a dose-related (5–20 mg/kg) potentiation of pentobarbitone sleeping time. In radioligand binding assays using 2-[¹²⁵I]iodomelatonin in chicken brain membranes, all of the analogues were competitive inhibitors. There was no correlation between their ability to inhibit 2-[¹²⁵I]iodomelatonin binding in chick and sedative potency in the mouse. Potentiation of pentobarbitone sleeping time by diazepam (1 mg/kg IP), but not melatonin (10 mg/kg IP), was blocked by pretreatment with the benzodiazepine antagonist, flumazenil (10 mg/kg IP). Similarly, an increase in pentobarbitone sleeping time produced by the aminoalkylindole cannabinoid receptor agonist, WIN 55212-2 (0.5 mg/kg IP), but not that produced by melatonin (10 mg/kg IP) was reduced by the cannabinoid receptor antagonist WIN 56098 (5 mg/kg IP). These studies confirm that melatonin has sedative activity and show that this action is shared by several structurally-related analogues but does not appear to be mediated by an interaction with benzodiazepine or cannabinoid receptors.     

Effect of cannabis on pentobarbital-induced sleeping time and pentobarbital metabolism in the rat

The effects of two cannabis extracts with different cannabinoid compositions, as well of as pure Δ¹-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD), on pentobarbital metabolism were studied in the rat. Extract I, with high proportions of CBN and CBD relative to THC, when given by gavage 21·5, 40 or 63 hr before pentobarbital (30 mg/kg, i.p.), prolonged the sleeping time by 53, 42 and 21 per cent respectively. This effect was paralleled by decreases in the rate of disappearance of [¹⁴C]pentobarbital from the blood, and of pentobarbital metabolism by liver microsomal preparations in vitro. Extract II, with low relative proportions of CBN and CBD, did not have any significant effect on penobarbital metabolism or sleeping time. CBD alone, in the same dose as that given in Extract I, had very similar effects, while a dose of CBD equivalent to that given in Extract II had no effect. THC, CBN and CBD added to normal rat liver microsomes in vitro inhibited pentobarbital metabolism competitively, CBD being a much more potent inhibitor than THC and CBN. The CBD content may, therefore, be a significant factor in interactions between marijuana and other drugs.     

腺苷A1受体新配体YZG-404的镇静催眠作用

目的研究新化合物YZG-404与腺苷A1受体（A1R）和腺苷A2A受体（A2AR）的亲和力及其镇静催眠作用。方法采用放射性配体受体竞争结合实验分别测定YZG-404与腺苷A1R和腺苷A2AR的亲和力;采用开阔场实验测定其对小鼠自发活动的影响;采用协同戊巴比妥钠睡眠实验评价其镇静催眠作用。结果 YZG-404对腺苷A1R亲和力较高,Ki值为98.8 nmol/L,而对腺苷A2AR的亲和力较低,Ki值约为9828.8 nmol/L。与溶剂对照组比较,YZG-404（1.25、2.5和5 mg/kg,ig）明显抑制小鼠的自发活动,抑制率分别为26.0%、59.7%和67.1%。另外,YZG-404（1.25、2.5和5 mg/kg,ig）可以明显延长戊巴比妥钠诱导小鼠睡眠时间,延长率分别为49.7%、129.5%和126.0%,并缩短入睡潜伏期,最高缩短率为19.8%。YZG-404能提高阈下剂量戊巴比妥钠诱导小鼠入睡率,最高入睡率达80%,效果与阳性对照药地西泮相当。结论新化合物YZG-404与腺苷A1R亲和力强,并具有强效的镇静催眠作用。     

吡唑并嘧啶类化合物的合成及其催眠作用的研究

目的设计并合成吡唑并嘧啶类化合物,并对其进行催眠作用研究。方法以乙酮类衍生物和N,N-二甲基甲酰胺二甲基缩醛为起始原料,再与3-氨基-4-氰基吡唑反应制备一系列吡唑并嘧啶类化合物;分别对阈下剂量戊巴比妥钠所致小鼠的催眠作用和阈上剂量戊巴比妥钠所致小鼠的催眠作用进行研究。结果设计并合成了7个目标化合物,其结构经~1H-NMR和ESI-MS确证。阈下剂量戊巴比妥钠所致小鼠的催眠作用研究表明化合物AL-5、AL-7有一定的协同戊巴比妥钠的催眠作用(P0.05),化合物AL-1、AL-3具有明显的催眠作用(P0.01)。阈上剂量戊巴比妥钠所致小鼠的催眠作用研究表明AL-1、AL-3、AL-5和AL-7组的睡眠持续时间均显著延长(P0.01、0.05),表明这些化合物有镇静催眠的效果。结论改进了吡唑并嘧啶类化合物的合成工艺,操作简单、成本低、产率较高;通过小鼠的行为学观察法对化合物的药效做了初步的评价,为今后的合成研究提供了方向。     

复方薰衣草颗粒镇静催眠及改善认知障碍作用研究

目的 观察复方薰衣草颗粒（CLG）镇静催眠及对轻度认知功能障碍（MCI）模型小鼠的治疗作用。方法 （1）CLG镇静催眠和抗抑郁、抗疲劳作用研究：以旷场训练结果为主要条件、体质量为次要条件，随机将79只ICR小鼠分为对照组、地西泮（3 mg·kg^-1，化药阳性药）组、复方枣仁胶囊（12.3 mg·kg^-1，中药阳性药）组和CLG低、中、高剂量（2.36、4.72、9.44 g·kg^-1）组。采用戊巴比妥钠阈下剂量催眠、旷场和转棒实验，观察CLG对小鼠的一般状态、睡眠潜伏期、30 min内入睡比例和总睡眠时间以及行为学的影响。（2）CLG改善MCI作用研究：将60只昆明小鼠以Y迷宫实验训练结果为主要条件、体质量为次要条件随机分为对照组、模型组、多奈哌齐（3 mg·kg^-1，阳性药）组和CLG低、中、高剂量（2.36、4.72、9.44 g·kg^-1）组，每天1次，连续ig给药14 d，给药第9天起，给药1 h后，除对照组外，ip 3 mg·kg^-1东莨菪碱制备MCI模型。于末次给药20 min后进行Y迷宫实验；第15天进行跳台实验；解剖取脑，称取脑质量并计算脑系数；HE染色后观察脑组织病理改变；取海马，ELISA法测定乙酰胆碱（Ach）、乙酰胆碱酯酶（AchE）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）水平。结果 （1）与对照组比较，CLG各剂量对体质量无明显影响；地西泮组和CLG各剂量组入睡率有增高趋势，但无显著性差异；地西泮组和CLG高剂量组入睡潜伏期明显缩短（P<0.05） ；各给药组睡眠时间均显著延长（P<0.01）。（2）与模型组比较，多奈哌齐组和CLG各剂量组跳台次数均显著减少（P<0.05）；CLG各剂量组Ach有升高趋势，多奈哌齐组和CLG中、高剂量组AchE有降低趋势；CLG各剂量组SOD显著增加，MDA显著降低（P<0.05）；CLG中、高剂量组小鼠皮层和海马病理改变明显减轻。结论 CLG具有镇静催眠作用，其改善MCI的作用可能与调节胆碱能系统和抗氧化应激有关。     

Sedation with promethazine profoundly affects spontaneous airway protection in sleeping neonatal piglets

1. Phenothiazine use in infants has been implicated in apparent life-threatening events, sleep apnoea and Sudden Infant Death Syndrome. 2. The aim of this study was to investigate the cumulative effects of a commonly used antihistamine medication containing promethazine on airway protective mechanisms and cardiorespiratory responses in 42 healthy neonatal piglets (21 naturally sleeping, 21 sedated sleeping). 3. Sedated piglets were given 1.5 mg/kg, p.o., promethazine 2 h prior to each recording session. Control animals slept naturally with no sedative given. On three consecutive days in all piglets, physiological recordings were made during sleep; on at least one of these days, simultaneous physiological and radiological observations were made. 4. Following sedation, sleep time and time in active sleep were increased significantly (P < 0.01). The spontaneous occurrence of swallowing, arousal, body movement, gastrooesophageal reflux and apnoea was compared between naturally and sedated sleeping piglets. Sedation with promethazine significantly decreased the spontaneous occurrence of swallowing (P < 0.05) and arousal (P < 0.05) and increased the occurrence of both central (P < 0.05) and obstructive sleep apnoea (P < 0.0001). 5. By the third day, a cumulative effect of promethazine was seen; the rate of swallowing and body movement significantly decreased (P < 0.01). 6. In summary, a low dose of promethazine profoundly altered sleep characteristics, airway protective mechanisms and cardiorespiratory responses in normal healthy sleeping piglets. Continued use of promethazine over several days may attenuate airway protective mechanisms to a potentially life-threatening degree. Our findings support continued caution in the use of promethazine-containing medications for the sedation of infants.