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Determination of five neurotransmitters in the rat brain for the study of the hypnotic effects of Ziziphi Spinosae Semen aqueous extract on insomnia rat model by UPLC-MS/MS

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Chinese Journal of Natural Medicines 2019年第7期17卷 551-560页

作者： YAN Yan LI Qiang DU Hui-Zhi SHEN Chen-Xi LI Ai-Ping PEI Xiang-Ping DU Chen-Hui QIN Xue-Mei Modern Research Center for Traditional Chinese Medicine Shanxi University Taiyuan 030006 China School of Chinese Materia Medica Shanxi University of Traditional Chinese Medicine Taiyuan 030619 China

Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.

关键词： Ziziphi Spinosae Semen Neurotransmitters UPLC-MS/MS hypnotic effects

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Remifentanil Has Sufficient hypnotic and Amnesic Effect for Induction of Anesthesia by Itself

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Open Journal of Anesthesiology 2014年第1期4卷 8-12页

作者： Takeshi Yokoyama Eiji Sakamoto Fumiyasu Yamasaki Koichi Yamashita Tomoaki Yatabe Kunio Suwa Department of Anesthesiology and Critical Care Medicine Kochi Med- ical School Hospital Nankoku Japan Department of Clinical La- boratory Kochi Medical School Hospital Nankoku Japan Department of Dental Anesthesiology Faculty of Dental Science Kyushu University Fukuoka Japan Teikyo Junior College Tokyo Japan

With a small-dose remifentanil, some patients showed no reaction and did not remember it postoperatively. We, therefore, hypothesized that remifentanil may decrease the level of consciousness and/or exhibit amnesic effect when stimulations are avoided. Thirty-patients were divided into two groups: non-stimulation group and stimulation group. Anesthesia was induced with 1 micro-g·kg?1·min?1 of remifentanil using no additional hypnotic agent. In the non-stimulation group, patients were left free from any stimulation except non-invasive blood pressure monitoring. In the stimulation group, patients were asked to follow verbal commands. The level of consciousness was evaluated with electroencephalogram and BIS-value derived from it. In the non-stimulation group, all patients reached the decreased level of consciousness in 5 minutes. In the stimulation group, however, 14 patients were judged to be still conscious. 10 patients could open their mouth at the 5th minute, but 9 of these 10 patients did not remember it postoperatively. In conclusion, remifentanil, with no additional anesthetics, exhibited hypnotic and amnesic effects when stimulations were kept minimal.

关键词： Remifentanil hypnotic potential Stimulation Amnesia

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A novel hypnotic compound,WS997,shortened NREM sleep latency and increased NREM sleep time in mice

A novel hypnotic compound,WS997,shortened NREM sleep latency...

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中国神经科学学会第十届全国学术会议

作者： Jing-Wen DONG Yuan SHI Li-Na TANG Jian-Jun ZHANG State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences ＆ Peking Union Medical College

Objective WS997 is a novel synthetic compound with hypnotic *** our previous study,WS997（60 mg/kg,i.p.） significantly shortened the sleep latency and prolonged the total sleep time in *** is a highly organized behavioral and physiologic state,which is typically defined based on either behavioral or electroencephalogram（EEG） characteristics and can be classified as one of two basic forms:the non-rapid eye movement（NREM） sleep and rapid-eye movement（REM） *** order to further characterize the effects of WS997on sleep-wakefulness patterns in mice,here we introduced the changes in EEG and EEG *** The EEG and electromyography（EMG） were simultaneously and continuously recorded for 7 h in freely moving mice in constant *** occurring in cortical EEG and sleep-wake states architecture were *** After injection of WS997（60 mg/kg,i.p.）,NREM sleep latency was significantly reduced compared to ***997（60 mg/kg,i.p.）increased NREM sleep,as well as the NREM sleep delta *** NREM sleep for 3 hours was increased from 80.9min to 174.5 min,and the increasing rate was 115.8%.The REM sleep was significantly decreased from 15.2 min to 4.7min,and the decreasing rate was 69.2%.EEG power was increased at delta frequencies（＜5Hz）,the peak increase being at 1-2 Hz,and was significantly decreased at higher frequencies（＞6 Hz）,which showed an inhibition pattern on the cortex *** WS997 exhibited clear-cut sleep-promoting effects in mice,including shortened NREM sleep latency and increased NREM sleep time.

关键词： sleep electroencephalogram non-rapid eye movement sleep-wake cycle hypnotic

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The hypnotic effect of lavender essential oil

The hypnotic effect of lavender essential oil

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中国睡眠研究会第九届学术年会

作者： Yu-Feng SHAO Le XIN Can WANG Jun-Fan XIE Min HOU Guang-Fu CUI Lin-Xin WANG Yi-Ping HOU Department of Neuroscience AnatomyHistology and EmbryologyKey Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical SciencesLanzhou University

Lavender essential oil（LEO） has been used to improving sleep and alleviating symptoms of anxiety in clinic *** effective characteristics and mechanisms involved in LEO action on sleep-wake cycle remain *** present study was undertaken to investigate the effect of intranasal delivering saturated LEO steam（SLEOS） on sleep-wake states and EEG power spectrums for 24 h（08:00-08:00 h） in *** of delivery parameter at 10 s SLEOS and 110 s fresh air（20ml/min）,compared to control,immediately enhanced the non-REM（NREM） sleep for 20 min（08:00-08:20 h,from 7.40 ± 1.78 min to 12.05 ± 1.07 min,P ＜ 0.05）and simultaneously accompanying a reduction in wakefulness（from 11.95 ± 2.03 s to 6.70 ± 1.23 s,P ＜ 0.05）,and increased REM sleep during 08:40-09:00 h（from 0.65 ± 0.31 minto 2.10 ± 0.46 min,P ＜ 0.05）.Near the end of light period（17:00-18:00 h）,SLEOS significantly increased non-REM（NREM） sleep during17:00-17:20 h（from 8.90 ± 1.76 min to 13.45 ± 0.27 min,P ＜ 0.05）,and REM sleep during 17:40-18:00 h（from 0.60 ± 0.26 min to 2.40 ± 0.52 min,P ＜ 0.01,） ***-induced enhancement of NREM and REM sleep was due to the increase of NREM and REM episode number,and reduction of wakefulness was because of a decrease in waking episode *** of each state across24-h sleep-wake cycle showed that SLEOS significantly decreased wakefulness（from 311.60 ± 8.99 min to 283.85 ± 5.94 min,P ＜ 0.05）,and increased rapid eye movement（REM） sleep（from 46.40 ±3.44 minto 56.10 ± 2.98 min,P ＜ 0.05） during light（inactive）period（08:00-20:00） and 24-h TST（from 75.15 ± 3.03 min to 85.40 + 3.42 min,P ＜ 0.05）.SLEOS-induced sleep mainly occurred during08:00-09:00 h andl7:00-18:00 *** significantly reduced the sleep latency in cage change（22.08 ± 3.24 min vs.43.20 ± 6.33 min,P ＜ 0.05） compared with control ***,olfactory epithelium lesion by intranasal application of zinc sulfate abolished the effect of the ***,the primary results show that SLEOS through olf

关键词： lavender essential oil hypnotic wakefulness rapid eye movement sleep non-rapid eye movement sleep

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The hypnotic effect of lavender essential oil and its potential pathways involved

The hypnotic effect of lavender essential oil and its potent...

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中国睡眠研究会第十一届全国学术年会

作者： Yufeng Shao Le Xin Chenchen Cai Xin Zheng Hailin Chen Yunong Chen Jinxian Gao Fengqiu Dai Guangfu Cui Junfan Xie Yiping Hou Department of Neuroscience Anatomy Histology and Embryology Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University

Objective Lavender essential oil（LEO） has been used to improving sleep and alleviating symptoms of anxiety in clinic practice. The effective characteristics and mechanisms involved in LEO action on sleep-wake cycle remain unclear. Methods The present study was undertaken to investigate the effect of intranasal delivering saturated LEO steam（SLEOS） on sleep-wake states and EEG power spectrums for 24 h（08:00-08:00 h） in mice. Results Odor of delivery parameter at 10 s SLEOS and 110 s fresh air（20 ml/min）, compared to control, immediately enhanced the non-REM（NREM） sleep for 20 min（08:00-08:20 h, from 7.40 ± 1.78 min to 12.05 ± 1.07 min, P ＜ 0.05） and simultaneously accompanying a reduction in wakefulness（from 11.95 ± 2.03 s to 6.70 ± 1.23 s, P ＜ 0.05）, and increased REM sleep during 08:40-09:00 h（from 0.65 ± 0.31 min to 2.10 ± 0.46 min, P ＜ 0.05）. Near the end of light period（17:00-18:00 h）, SLEOS significantly increased non-REM（NREM） sleep during 17:00-17:20 h（from 8.90 ± 1.76 min to 13.45 ± 0.27 min, P ＜ 0.05）, and REM sleep during 17:40-18:00 h（from 0.60 ± 0.26 min to 2.40 ± 0.52 min, P ＜ 0.01） again. SLEOS-induced enhancement of NREM and REM sleep was due to the increase of NREM and REM episode number, and reduction of wakefulness was because of a decrease in waking episode duration. Amount of each state across 24-h sleep-wake cycle showed that SLEOS significantly decreased wakefulness（from 311.60 ± 8.99 min to 283.85 ± 5.94 min, P ＜ 0.05）, and increased rapid eye movement（REM） sleep（from 46.40 ± 3.44 min to 56.10 ± 2.98 min, P ＜ 0.05） during light（inactive） period（08:00-20:00） and 24-h TST（from 75.15 ± 3.03 min to 85.40 ± 3.42 min, P ＜ 0.05）. SLEOS-induced sleep mainly occurred during 08:00-09:00 h and17:00-18:00 h. SLEOS significantly reduced the sleep latency in cage change（22.08 ± 3.24 min vs. 43.20 ± 6.33 min, P ＜ 0.05） compared with control group. Olfactory epithelium lesion by intranasal application of zinc sulfate abolished the effect of the SLEOS. Moreove

关键词： lavender essential oil hypnotic wakefulness rapid eye movement sleep non-rapid eye movement sleep orexin

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NHBA exerts potent sedative hypnotic effects in mice via suppressing the phosphorylation of CaMKII

NHBA exerts potent sedative hypnotic effects in mice via sup...

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中国神经科学学会第十届全国学术会议

作者： Li-Na TANG Yuan SHI Jing-Wen DONG Ying ZHANG Jian-Jun ZHANG State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College

Objective The levels of calcium/calmodulin kinase Ⅱ(CaMKH) and phosphorylated CaMKII expression are critically involved in the regulation of sleep and wakefulness(W).Activation of intracellular CaMKII signaling in the PPT promotes W and suppresses *** signaling pathways also has a cross-talk with *** adenylyl cyclase(AC) activation enables a persistent increase in the levels of autophosphorylated CaMKII.N

关键词： calcium/calmodulin kinase Ⅱ sedative hypnotic locomotor activity PKA

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Double-blind randomized controlled study of the efficacy, safety and tolerability of eszopiclone vs placebo for the treatment of patients with post-traumatic stress disorder and insomnia

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World Journal of Psychiatry 2020年第3期10卷 21-28页

作者： Sheila M Dowd Alyson K Zalta Helen J Burgess Elizabeth C Adkins Zerbrina Valdespino-Hayden Mark H Pollack Department of Psychiatry and Behavioral Sciences Rush University Medical CenterChicagoIL 60601United States Department of Psychological Science University of California IrvineIrvineCA 92697United States Sleep and Circadian Research Laboratory Department of PsychiatryUniversity of MichiganAnn ArborMI 48109United States Center for Behavioral Intervention Technologies|Department of Preventive Medicine Northwestern University Feinberg School of MedicineChicagoIL 60611United States Department of Psychology Montclair State UniversityMontclairNJ 07043United States

BACKGROUND Sleep disturbance is a core feature of post-traumatic stress disorder(PTSD).Given the relationship between sleep disturbance and PTSD,there has been a relative paucity of studies examining the potential therapeutic impact of using pharmacotherapy to target sleep disturbance in patients with ***(ESZ)is a non-benzodiazepine y-aminobutyric acid-A receptor agonist indicated for the treatment of sleep and may affect sleep in patients with *** To evaluate the efficacy of ESZ vs placebo(PBO)for patients with PTSD and *** The study was a 12-wk,double blind,randomized controlled trial with 3 mg of ESZ(n=13)or PBO(n=12).RESULTS Patients in both arms experienced significant improvement in PTSD symptoms as assessed by the Clinician-Administered PTSD Scale for DSM-IV(CAPS):ESZ(t11=-3.12,P=0.005)and PBO(t11=-3.5,P=0.002)and by self-report with the Short PTSD Rating Interview(ESZ t11=-3.38,P=0.003 and PBO t11=-4.48,P=0.0005).There were no significant differences between treatments on the CAPS(t22=-0.13,P=0.70)or the Short PTSD Rating Interview(t22=-0.58,P=0.56).Similarly,both treated groups improved on sleep measures as assessed by the Pittsburgh Sleep Quality Index with PTSD Addendum(PSQI)and on total sleep time(TST)and sleep latency assessed by actigraphy with no significant differences between groups(PSQI t22=-0.24,P=0.81;total sleep time t10=0.13,P=0.90 and sleep latency t10=0.68,P=0.50).There was a significant correlation between improvement in sleep and overall improvement in PTSD as measured by change scores on the PSQI and CAPS,r(8)=0.79,P=0.01 for ESZ treated subjects,but not for those treated with PBO r(9)=0.16,P=*** events of ESZ were consistent with the known profile of the medication including dysgeusia(30%,mild),sedation(20%,mild)and headache(20%,moderate to severe).CONCLUSION Results do not support the hypothesis of a specific positive effect of ESZ compared to PBO for measures of PTSD and associated sleep disturban

关键词： Trauma Sleep disturbance hypnotic Post-traumatic stress disorder

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A COMPARATIVE STUDY OF IMOVANE AND ESTAZOLAM TREATMENT ON SLEEP DISTURBANCES

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Chinese Medical Sciences Journal 1995年第1期10卷 56-58页

作者：李舜伟王长华 Department of Neuropsychiatry PUMC Hospital Beijing.

Twentysix Patients with sleep disturbances who had completed therapy with hypnotics were observed under single-blind and self-comparable method for 7 days each. We found that patients treated with imovane or estazolam had no statistical differences with respect to sleep time onset. total sleep time. nocturnal awakening. feeling after awakening, dream, drug side effects and sleep *** performed better than estazolam in sleep time onset and total sleep time. From this study, imovane can he recommended as a new hypuotic to treat patients with sleep disturbances.

关键词： imovane estazolam hypnotic sleep disturbance

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Investigation of the usefulness of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function

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Journal of Medical Colleges of PLA(China) 2016年第1期31卷 28-33页

作者： Liang-En Chen An-Dong Zhao Qing-Jun Zhang Feng Wu Zhao-Li Ge Hua Ge Hao Zhan Department of Pharmacology Institute of Aviation MedicineAir Force

Background:Military operation personnel often suffer from sleep difficulty because of their work *** this study,we investigated the efficacy of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function; we subsequently established the optimal dosage regimen for military operation ***:Twenty-two healthy young male volunteers were recruited for the *** subjects took 10 mg or 15 mg of zaleplon and placebo alternately and then were exposed to *** in polysomnography(PSG) indices,including sleep latency(SL),sleep efficiency(SE) and sleep structure,were recorded after drug *** awakening,the volunteers' subjective judgments of sleep quality and sleepiness were *** volunteers underwent 3 psychomotor performance tests at a one-week interval,and the psychomotor performance tests were conducted before and after taking zaleplon and *** volunteers participated in the vestibular function test session,and parameters,including optokinetic nystagmus(OKN),vestibular ocular reflex(VOR),visualvestibular ocular reflex(VVOR) and vestibular ocular reflex fixation suppression(VOR-Fix),were detected by the same experimental design as described *** data of sleep observations were subjected to one-way variance ***:Compared with the placebo group,SL was shortened significantly,and the scores of subjective sleep quality and sleep depth were clearly increased in the zaleplon 10 mg group(P<0.05).Moreover,the SE and the percent of REM(rapid eye movement) sleep were increased remarkably in the zaleplon 15 mg group(P<0.01).Furthermore,the SE,percent of REM sleep and scores of subjective sleep depth in the zaleplon 15 mg group were significantly higher than in the zaleplon 10 mg group(P<0.05).The psychomotor performance did not change significantly after ingestion of 10 mg or 15 mg of zaleplon,whereas the OKN and VOR gains

关键词： Insomnia Sleep hypnotic Zaleplon Psychomotor performance Vestibular function

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Psychopharmacological Profile of Hydroalcoholic Extract and P-Hydroxybenzoic Acid Obtained from <i>Bourreria huanita</i>(Boraginaceae) in Mice

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Pharmacology & Pharmacy 2014年第11期5卷 983-995页

作者： Iandra Holzmann Daiane Cattani Micheli Corso Daiane Perondi Sabrina Zanella Cristiani Burger Luiz Carlos Klein Júnior Valdir Cechinel Filho Sully M. Cruz Miguel F. Torres Armando Cáceres Márcia Maria de Souza Programa de Pós-Graduação em Ciências Farmacêuticas Universidade do Vale do Itajaí Itajaí Brazil Núcleo de Investigações Químico Farmacêuticas Universidade do Vale do Itajaí Itajaí Brazil Facultad de CCQQ y Farmacia Universidad de San Carlos Guatemala City Guatemala

Bourreria huanita (Lex.) Hemsl. (Boraginaceae) is a very rare and highly appreciated tree in Mesoamerica for its medicinal properties and beauty. It grows in a region extending from central Mexico to Costa Rica. Ethnobotanical surveys have shown that the infusion of dried flowers is popularly used as a tranquilizer to cure several diseases. In the present study we report the isolation of p-hydroxybenzoic acid (pHBZ) obtained from the hydroalcoholic extract (HE) of B. huanita, and the effect of both, the extract and the compound on the central nervous system in mice. HE of B. huanita (100, 150, 300 mg/kg) and pHBZ (10 mg/kg) were orally administered to mice and 1 h later, behavioral tests were performed. The effects of HE and pHBZ were tested by pentylenetetrazole (PTZ) and strychnine (STR) induced seizures, pentobarbital-induced hypnosis, the forced swimming test and the tail suspension test, the elevated plus maze, apomorphine-induced stereotypy and the climbing test, the inhibitory avoidance test and the open-field test. B. huanita extract produced hypnotic, anxiolytic and antidepressant effects in animals, with no change in motor performance. On the other hand, the extract did not reduce PTZ and STR-induced convulsions, apomorphine-induced stereotypy or climbing. Moreover, no changes were observed in the animals’ memory. The compound pHBZ was effective only in the depression tests. The results obtained in the present study suggest that B. huanita exhibited sedative, antidepressant and hypnotic activities in mice, and that the antidepressant activity may be mediated by an isolated compound identified as pHBZ.

关键词： Bourreria huanita Antidepressant Sedative and hypnotic Activities P-Hydroxybenzoic Acid

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