• The Korean Journal of Pain
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• v.28 no.1
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• pp.4-10
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• 2015

Etifoxine (etafenoxine, $Stresam^{(R)}$) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by $GABA_A{\alpha}2$ receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to ${\beta}2$ or ${\beta}3$ subunits of the $GABA_A$ receptor complex. It also modulates $GABA_A$ receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates $GABA_A$ receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.4
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• pp.823-829
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• 1997

The patients visiting pediatric dental office have been being younger than the previous, and they were often combined with systemic disease. But, we aren't able to perform the verbal communication, because of their impediment and youthfullness. And, we can't carry out the behavior control via physical restraint, as the developed social structure and the attitude of children and their parents. So, the importance and concerning of conscious sedation using sedative medicine are increased by time and time. Among the various conscious sedation, Chloral Hydrate and Nitrous Oxide inhalation are most popularly used, and barbiturates, benzodiazepine, opioids and hydroxyzine are used often. But, these medications have some side-effects and adverse reactions, may be failed to sedate the children. And limited use of medically compromised patients, especially for ASA class III, IV or more dangerous patients. We, the Department of Pediatric Dentistry, Chosun University have met some dangerous situation due to unfavorable pharmacogenic reactions, but we can control the situation and get well healed results. The below results are common situations and their solutions during conscious sedation. 1. By the intravenous administration, thrombophlebitis is the most common side-effects, but it may be healed with time without any special treatment. 2. Under the definitive guidelines about conscious-sedation, we can perform a safe conscious sedation for ASA class III patients. 3. When adversed reaction of Benzodiazepine is occured, it could be cared effectively with benzodiazepine antagonist, named Flumazenil.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.11 no.2
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• pp.76-80
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• 2015

Mental retardation is one of the major disorders covered in special care dentistry. Patients show poor oral health and are a challenge for the dentist due to lack of cooperation. Triazolam is a short-acting benzodiazepine and has been used in the dental office for many years because of its favorable properties. In this study, five patients with mental retardation were sedated with triazolam on a dental out-patient setting. Patients were administrated with 0.25 mg or 0.5 mg of triazolam on the first dose according to the patient's cooperation. Twenty minutes after the initial dose, patients received 0.25 mg of triazolam. Triazolam was administrated sublingually to one patient and orally to four patients. Hydroxyzine was also administrated to three patients in order to prevent nausea and vomiting. All patients were inhaled with 50% nitrous oxide during the sedation. Treatment time ranged from 20 minutes to 55 minutes. Two patients showed paradoxical reactions and were administrated with intramuscular injections of flumazenil. In result, depending on the range of dental treatment and level of intellectual disability, we can assume that triazolam may be beneficial for sedation in disabled patients.

• Korean Journal of Pharmacognosy
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• v.35 no.1 s.136
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• pp.22-27
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• 2004

Scutellaria baicalensis Georgi is one of most important medicinal herbs in traditional chinese medicine. The object of this study was to determine the effects of the water extracts of Scutellaria baicalensis (SB) on the anxiolytic-like activities in the elevated plus-maze (EPM) test. The watεr extracts of SB (100, 200, or 400 mg/kg) were orally administered to male SD rats for 3 days, and behavioral tests for the anxiolytic activity were performed. SB (100, 200, or 400 mg/kg) significantly increased in time-spent and arm entries into the open arms of the EPM compared with the control group. Futhermore, those anxiolytic-like activities of SB were antagonized by flumazenil (a $GABA_A$ antagonist, 3 mg/kg), but not by pindolol (a $5-HT_{1A}$ antagonist, 10 mg/kg). SB did not cause myorelaxant effects in the horizontal wire test at any dosage regimen. Therefore, these findings suggest that SB promote the anxiolytic-like activity mediated by GABAergic nervous system in rats.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.819-829
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• 2022

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABA_A antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABA_A receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.1
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• pp.21-27
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• 2008

Purpose: The aim of this survey was to analyze the choice of sedative drugs and their side effects during pediatric endoscopic sedation in Korea. We also evaluated doctors, caretakers and patient satisfaction with the procedures. Methods: Between June 2006 and July 2006, a 16-item survey regarding current sedation practices, during one month, was mailed to 28 hospitals in Korea. The results of the survey responses were then analyzed. Results: Endoscopy performed under conscious sedation was reported in 89.0% of the responders and endoscopy under general anesthesia in 0.9% of 465 endoscopic procedures. Endoscopy under conscious sedation was performed in 89.1% for upper gastrointestinal endoscopy (GFS) and 88.1% for lower GFS. Midazolam was used for conscious sedation during the endoscopy in 84.5% of cases and propofol was used in two cases (0.5%). In addition, a bezodiazepine/opioid combination was used iin 84.6% (44 cases) for lower GFS. Patients were monitored with pulse oxymetry, EKG (91.4%) as well as automatic BP (5.1%). Transient hypoxia was the only side effect noted and was treated with supplemental oxygen (4.6%). Flumazenil was used in 2.71% of cases. The choice of sedation was made by the endoscopist (84%). The satisfaction rate for endoscopists was 68%, and for the patients and caretakers was 84% (as reported by the endoscopists). Conclusion: Midazolam was used only for the upper GFS and benzodiazepine/opioid combination was used for the lower GFS in Korea. The rate of satisfaction was relatively high and there were no significant side effects noted during the endoscopy under conscious sedation.

• Journal of the korean academy of Pediatric Dentistry
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• v.47 no.1
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• pp.53-61
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• 2020

Midazolam is a short-acting benzodiazepine that is widely used in pediatric dental sedation. However, its clinical effectiveness as an intravenous sedative agent in children has not been widely documented. A retrospective study was conducted to evaluate the efficacy and safety of intravenous midazolam and nitrous oxide inhalation sedation in pediatric dental treatment. The subjects were 115 patients (118 cases) who received dental treatment under intravenous midazolam and nitrous oxide inhalation sedation. Demographic factors, general health status, sedation time, midazolam and nitrous oxide dosage, and success rate of sedation were evaluated from electronic medical records. Behavioral management was the main reason of choosing sedation. Mean duration of sedation was 56.7 minutes for surgical treatment, and 74.4 minutes for restorative treatment. The initial dosage of intravenous midazolam was 0.051 ± 0.019 mg/kg. In 34 cases (28.8%), additional midazolam of 0.036 ± 0.057 mg/kg was delivered during the treatment. The concentration of nitrous oxide was maintained between 40% and 50%. The success rate of sedation was 99% (n = 117). In 1 case, laryngospasm occurred and the patient was reversed with benzodiazepine antagonist, flumazenil. Intravenous midazolam sedation with nitrous oxide was shown to be clinically effective for the dental treatment in children, if administered by trained personnel and patients are carefully selected in accordance with guidelines.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.769-774
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• 1997

Non-neuronal high affinity binding sites for benzodiazepines have been found in many peripheral tissues including cardiac muscle and vascular smooth muscle, and have been designated as 'peripheral benzodiazepine receptor'. Benzodiazepines have been shown to induce relaxation of the ileal, vesical, and uterine smooth muscles. However, it is still unclear about possible involvement of peripheral benzodiazepine receptor on the contractility of trachealis muscle. This study was performed to investigate the role of the peripheral benzodiazepine receptor on the contractility of canine trachealis muscle. Canine trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiological salt solution maintained at $37^{\circ}C$, and aerated with $95%\;O_2/5%\;CO_2$. Isometric myography was performed, and the results of the experiments were as follows: Ro5-4684, FGIN-1-27 and clonazepam reduced a basal tone of isolated canine trachealis muscle strip concentration dependently, relaxant actions of RoS-4684 and FGIN-1-27 were antagonized by PK11195, a peripheral benzodiazepine receptor antagonist. Flumazenil, a central type antagonist, did not antagonize the relaxant action of Peripheral type agonists. Saturation binding assay of [3H]Ro5-4864 showed a high affinity$(Kd=5.33{\pm}1.27nM,\;Bmax=\;867.3{\pm}147.2\;fmol/mg\;protein)$ binding site on the canine trachealis muscle. Ro 5-4684 suppressed the bethanechol-, 5-hydroxyoyptamine- and histamine- induced contractions. Platelet activating factor (PAF) exerted strong and prolonged contraction in trachealis muscle strip. Strong tonic contraction by PAE was attenuated by Ro 5-4684, but not by WEB 2086, a PAF antagonist. Based on these results, it is concluded that the peripheral benzodiazepine receptor mediates the inhibitory regulation of contractilty of canine trachealis muscle.

• Journal of The Korean Society of Clinical Toxicology
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• v.4 no.1
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• pp.32-43
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• 2006

Purpose: Toxic Exposure Surveillance System (TESS) is widely used for poisoning data collection and making a counterplan. But, there were few reports about poisoning data collection using TESS in Korea. The aim was to collect poisoning data using TESS report form and investigate the recognition of emergency physician about the necessity of TESS as preliminary survey. Methods: Retrospectively, we gathered data from hospital records about the patient who admitted hospital emergency room due to poisoning. Date were gathered by paper and/or web client system report form in patients recruited by ICD-10 codes Results: From Jun 2004 to May 2005,3,203 patients were enrolled in 30 hospitals and their mean age was $44.9{\pm}20.3years$ old(male: female = 1,565: 1,638). The most frequent site of exposure was their own residence (73.2%, 2,345/3,203) and most of reported patients were older than 20 years(89.7%, 2,871/3,203). Frequent substances involved in poisoning were medication(41.9%) and pesticide(33.3%). Intentional poisoning was 60.7%(1,954). In fatality, overall frequency was 5.1%(162/3,203) and the most frequent route of exposure was ingestion(96.3%, 156/162) and the most frequent substance was pesticide(85.2%, 138/ 162). Antidotes were administered in 202 patients(2-PAM, atropine, antivenin, N-acetylcystein, vitamin K, flumazenil, ethanol, methylene blue, naloxone, calcium compound). 19 of 20 emergency physicians agreed with necessity of TESS. Conclusion: Data collection using TESS report form showed preliminary poisoning events in Korea. Frequent poisoning substance were medication and pesticide. The fatality was mainly related with pesticide ingestion. Many doctors in emergency room recognized the necessity of TESS.