• Title/Summary/Keyword: flumazenil

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Anxiolytic Effects of Quercetin: Involvement of GABAergic System (Quercetin의 항불안 효과: GABA 신경계를 중심으로)

  • Jung, Ji Wook;Lee, Seungheon
    • Journal of Life Science
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    • v.24 no.3
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    • pp.290-296
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    • 2014
  • The present experiment investigated putative anxiolytic-like effects of quercetin using an elevated plus-maze (EPM) and hole-board apparatus test in mice. Quercetin is a flavonoid widely distributed in nature. Quercetin (1.25, 2.5, 5, or 10 mg/kg) was orally administered to ICR mice 1 h before a behavioral evaluation in the EPM. Control mice were treated with an equal volume of vehicle, and positive control mice were treated with buspirone (2 mg/kg, i.p.). The mice administered quercetin (5 mg/kg) spent a significantly longer percentage of time in the open arms of the EPM and their percentage of entries into the open arms was significantly increased compared to the vehicle-treated controls (p<0.05). The anxiolytic-like activities of quercetin were antagonized by trans-4-aminocrotonic acid (a $GABA_{A-{\rho}}$ agonist, 20 mg/kg) but not by flumazenil (a $GABA_A$ antagonist, 10 mg/kg) or WAY-100635 (a $5-HT_{1A}$ antagonist, 0.3 mg/kg). Moreover, there were no changes in the locomotor activity or myorelaxant effects in any group compared with the vehicle-treated controls. In the hole-board apparatus test, the number of head-dips increased significantly in the single treatment with quercetin (5 mg/kg) group compared to the vehicle-treated controls (p<0.05). These findings suggest that quercetin can promote anxiolytic-like activity, mediated by the GABAergic nervous system, in mice.

Anxiolytic-like Effects of Saponin and Polysaccharide Fractions Extracted from White and Red Ginsengs in the Elevated Plus-Maze Model

  • Kim, Tae-Woo;Choi, Hyuck-Jai;Kim, Nam-Jae
    • Journal of Ginseng Research
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    • v.31 no.4
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    • pp.217-221
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    • 2007
  • Ginseng has been widely used for the management of anxiety and emotional instability, but there is little experimental evidence supporting these clinical applications. The anxiolytic-like effect of ginseng saponin and polysaccharide fractions of white (WG) and red ginsengs (RG) was investigated using the elevated plus-maze test. The saponin (SF) and polysaccharide (PF) fractions were orally administered to male ICR mice for 3 days and behavioral test for the anxiolytic activity were performed. SF significantly increased the time-spent open arms and number into the in the open arm entries. However, PF weakly increased the time-spent in the open arms, but did not increase number into the open ann entries. The WG showed more potent anxiolytic-like effect than that of RG. The anxiolytic-like activities were antagonized by flumazenil, but not by esmolol. These findings suggest the saponin fractions of WG and RG promote the anxiolytic-like activity by antagonizing GABN/benzodiazepine receptors in mice.

Paradoxical Reaction to Midazolam Used in Intravenous Sedation for Dental Treatment -Report of a Case and Review of the Literature- (치과치료를 위한 정주진정법에 사용되는 미다졸람에 대한 역설적 반응 -증례 보고 및 문헌고찰-)

  • Jeon, Jae-Yun;Jung, Se-Hwa;Lee, Byung-Ha;Im, Jae-Jung;Hwang, Kyung-Gyun;Shim, Kwang-Sup;Park, Chang-Joo
    • Journal of The Korean Dental Society of Anesthesiology
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    • v.9 no.2
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    • pp.104-107
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    • 2009
  • Midazolam, one of the most common benzodiazepine derivatives, is widely used in intravenous sedation for dental treatment without severe complications. However, paradoxical reactions to midazolam, including patient's unanticipated restlessness, agitation, hostility, and rage, have been frequently reported since the introduction of benzodiazepine. During outpatient intravenous sedation using midazolam for dental treatment, we experienced a paradoxical reaction to midazolam in a 28-year-old female patient. With a thorough review of the literature, the management of this complication and its various etiologies were discussed.

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Isolation of a sleep-promoting compound from Polygonatum sibiricum rhizome

  • Jo, Kyungae;Kim, Hoon;Choi, Hyeon-Son;Lee, Seung-Su;Bang, Myun-Ho;Suh, Hyung Joo
    • Food Science and Biotechnology
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    • v.27 no.6
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    • pp.1833-1842
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    • 2018
  • The aim of this study was to identify sleep-promoting substance from Polygonatum sibiricum rhizome extract (PSE) with the regulation of sleep architecture. PSE showed a decrease in sleep latency time and an increase in the sleeping time. In the electroencephalography analysis of rats, PSE (150 mg/kg) showed an increase of non-rapid eye movement by 38% and a decrease of rapid eye movement by 31% compared to the control. This sleep-promoting activity was found to be involved in the $GABA_A$-BDZ receptor. The chemical structure of the pure compound was determined by the $^1H$ and $^{13}C$ nuclear magnetic resonance spectroscopy and gas chromatography mass spectrometry analysis; active compound was glyceryl-1-monolinoleate. The commercial standard glyceryl-1-monolinoleate showed a similar inhibitory concentration on [$^3H$]-flumazenil binding to $GABA_A$-BDZ receptors with final active fraction of PSE. The results indicate that glyceryl-1-monolinoleate is a major active compound responsible for the PSE-derived sleep promotion.

The Action Mechanism of Diazepam on the Contractility of Canine Trachealis Muscle (개의 기관근 수축성에 대한 Diazepam의 작용기전)

  • 권오철;최은미;최형철;김용대;하정희;서장수;이광윤
    • Korean Journal of Bronchoesophagology
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    • v.4 no.1
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    • pp.64-72
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    • 1998
  • This study aimed at observing the effect of diazepam on the contractility of trachealis muscle isolated from canine trachea, possible involvement of central or peripheral type benzodiazepine receptor, and the calcium related mechanism of action of diazepam. Trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiologic salt solution maintained at $37^{\circ}C$, and aerated with 95% $O_2$ /5% $CO_2$. Isometric myography was performed. Diazepam reduced the basal tone concentration dependently, and this inhibitory action was not affected by neither flumazenil, a central benzodiazepine receptor antagonist, nor PK11195, a peripheral benzodiazepine receptor antagonist. Pretreatment with diazepam showed the inhibitory effect on the concentration-response curves to agonists such as bethanechol, 5-hydroxytryptamine and histamine. Diazepam also caused concentration-related inhibition of contraction with potassium chloride 30 mM. The effect of diazepam on the basal tone and potassium chloride-induced contraction with calcium channel blockers were compared. Similar results were obtained in canine trachealis with verapamil, nifedipine and diltiazem. These results suggest that diazepam relax an airway muscle not via specific receptors but by a similar action as calcium channel blockers in canine trachealis muscle.

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Type Analysis of Drug Intoxicated Patients in Daegu Emergency Medical Center and Medical Flexibility of Diagnostic Test Using Drug Addiction Selecting Kit

  • Lee, Seung-Jin;Lim, Soon-Ok;Kim, Tae-Jeong;Park, Min-Jeong;Ryu, Jong-Ha
    • Korean Journal of Clinical Laboratory Science
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    • v.45 no.3
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    • pp.91-95
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    • 2013
  • It is important to check the types of drugs when treating acute drug intoxication. This study researches the clinical characteristics and types of patients hospitalized in emergency medical center for drug addiction in 2009 and 2010. By applying a drug addiction selecting kit, it studied the flexibility and clinical efficiency during diagnosis and treatment. The study result shows, among the drugs causing addiction, Sedative accounts for 34.4%, Herdicide 23.5%, Analgesic 17.2%, Insectide 7.8% and else 17.2%. Sedative showed the highest proportion both in 2009 and 2010. Among the drug addicted patients, 39 cases did not know that the drugs are poisonous and among them, the drug addiction selecting kit was positive in 32 cases (82.0%). In 42 cases where addiction was suspicious, 25 cases (59.5%) were positive in the drug addiction selecting kit. In 57 cases of using drug addiction selecting kits, the cases in which benzodiazepine was positive, were 30 and the most frequently cases were as follows; Tricyclic Antidepressants (TCA) 13 cases, Amphetamines 3 cases, barbiturate 3 cases, and piate 3 cases. In the district using drug addiction kit meaningfully had Flumazenil injection much greater impact than the one not using the kit. This proves the efficiency of the kit (p<0.05). The uses of drug addiction selecting kits are for acute drug intoxicated patients and for providing objective and scientific information when emergency medical doctor are checking unchecked poisoning drugs. It is considered that drug addiction selecting kits would give help when treating the early stage of drug addicted patients in emergency medical treatment.

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Flavonoid in Clover Honey Exerts a Hypnotic Effect via Positive Allosteric Modulation of the GABAA-BZD Receptor in Mice

  • Han, Kyoung-Sik;Yang, Hyejin;Yoon, Minseok
    • The Korean Journal of Food And Nutrition
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    • v.30 no.6
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    • pp.1364-1369
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    • 2017
  • There is a growing demand for natural sleep aids due to various side effects of long-term administration of pharmacological treatments for insomnia. Honey has been reported to exhibit numerous potential health benefits, and it is hypothesized that honey may favorably affect insomnia treatment. Therefore, this study was performed to investigate the possible hypnotic effect of clover honey (CH) and to determine its in vivo mechanism. The total flavonoid content (TFC) of CH and fractions extracted with ethylacetate (EtOAc) and $H_2O$ was measured. The pentobarbital-induced sleep test using $GABA_A$-benzodiazepine (BZD) agonists and antagonists was conducted to evaluate the potential mechanism of action behind the sedative-hypnotic activity of CH in mice. The results showed that administration of 500 and 1,000 mg/kg of CH significantly (p<0.01) reduced the sleep latency to a level similar to that of diazepam (DZP, 2 mg/kg), and 1,000 mg/kg of CH significantly (p<0.01) prolonged the sleep duration, which was comparable to that of DZP (2 mg/kg). Administration of the EtOAc fraction with a higher TFC significantly reduced the sleep latency at 50 to 200 mg/kg and prolonged the sleep duration at 100 to 200 mg/kg, which were comparable to those after administration of DZP (2 mg/kg). However, co-administration of CH and EtOAc with flumazenil, a specific $GABA_A-BZD$ receptor antagonist, blocked the hypnotic effect. Our findings suggest that the hypnotic activity of CH may be attributed to allosteric modulation of $GABA_A-BZD$ receptors. The TFC of CH is expected to be a key factor that contributes to its hypnotic effect.

Anti-stress Activities of Ginsenoside Rb1 is Related with GABAnergic Neuron

  • JUNG In Kyung;LEE Sook Yeon;PARK Il Ho;CHEONG Jae Hoon
    • Biomolecules & Therapeutics
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    • v.13 no.3
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    • pp.165-173
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    • 2005
  • The main aim of this study was to investigate stress related activities of ginsenosides and their action mechanism. Control group and ginsenoside supplemented groups were exposed to stress while no-stress group was not done. Animals of each group (n=$8\~10$) were orally administerd 100 mg red ginseng extract (R-G), or 10 mg ginsenosides/kg body weight once a day. Animals were given materials for 5 days without stress, and then were given supplements for 5 days with restraint and electroshock stress. Mice were given materials for 5 days for experiments on anti-fatigue effect. After loading final stress, stress-related behavioral changes of experimental animals were examined and plasma corticosterone levels were measured. R-G and ginsenoside $Rb_{1}$ supplementation partially blocked the stress effects on locomotion and elevated plus-maze test in rats and mice. They also partially blocked stress induced behavioral changes such as freezing, smelling, face-washing, rearing behavior in rats. R-G and $Rb_{1}$ decrease adrenal gland size and plasma corticosterone level, which were increased by stress in rats. R-G increased enduring time on the Rota rod, cold water and horizontal wire, but $Rb_{1}$ didn't. Effects of $Rb_{1}$ on plusmaze test were inhibited by administration of flumazenil. These results suggest that $Rb_{1}$ is the main antistress principle in ginseng and it's effect is modulated by GABAnergic nervous system.

Anxiolytic Effects of Woohwangcheongsimwon in Mice

  • Yoon, Byung-Hoon;Kim, Dong-Hyun;Lee, Seung-Joo;Shin, Bum-Young;Lee, Yong-Hyuk;Kim, Dong-Hee;Park, Chan-Sung;Lee, Yong-Wook;Cho, Hi-Jae;Yamamoto, Yutaka;Kang, Dong-Hyo;Ryu, Jong-Hoon
    • Natural Product Sciences
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    • v.15 no.3
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    • pp.115-120
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    • 2009
  • Woohwangcheongsimwon (WHCSW) is a traditional oriental medicinal fomula which has been clinically used for treating strokes, palpitation, loss of consciousness and anxiety. The purpose of this study was to characterize the putative anxiolytic properties of WHCSW using an elevated plus-maze (EPM) and hole-board test. Control mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). In the EPM test, WHCSW significantly increased the percentage of time-spent in the open arms (200 mg/kg, P < 0.05) and the percentage of open arm entries (200 and 400 mg/kg, P < 0.05). WHCSW also significantly increased the number of head-dips in the hole-board test (200 mg/kg, P < 0.05). In addition, the anxiolytic properties of WHCSW examined in the EPM test were inhibited by flumazenil (10 mg/kg, i.p.), a GABA$_A$ antagonist. However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus 10% Tween 80 controls. These results suggested that WHCSW is an effective anxiolytic agent, and that its anxiolytic effects are mediated via GABA$_A$ receptors.

Studies on the Behavioral Pharmacology of the Antidepressant Effect of Polygala japonica Houtt (영신초(靈神草)의 항우울 효과에 대한 행동약리학적 연구)

  • Lee, Eun-Kyung;Chung, Dae-Kyoo
    • Journal of Oriental Neuropsychiatry
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    • v.22 no.2
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    • pp.129-146
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    • 2011
  • Objectives : The purpose of this study was to characterize the putative antidepressant and antianxiolytic effects of the 70% ethanol extract of Polygala japonica(EEPJ) using animal's behavioral experiment in mice. Methods : The effect of EEPJ on the anxioty and depressive disorder was investigated via mice's behavioral experiment like Elevated plus-maze, Horizontal wire test, Open field test, Forced swimming test, Tail suspension test, and it was happen via any mechanism by WAY 100635, a 5-HT1A receptor antagonist and by Flumazenil, a GABAA antagonist Results : 1. In the EPM, single treatments of the EEPJ(200 and 400mg/kg) had usefully antianxiolytic effects versus vehicle, which was medicated via the serotonergic nervous system. 2. In the HWT, single treatments of the EEPJ were no changes in the myorelaxant effects versus vehicle. 3. In the OFT, single treatments of the EEPJ were no changes in the locomotor activity versus vehicle. 4. In the FST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. 5. In the TST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. Conclusions : These results indicate that EEPJ is an effective antidepressant and antianxiolytic activity in mice, and it might be usefully applied for prevention and treatment of depressive disorder through evolutive study like development of various experimental models.