• The Korean Journal of Pain
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• 제28권1호
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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.

• 대한화학회지
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• 제55권4호
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• pp.638-643
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• 2011

Silica sulfuric acid (SSA)를 이용하여 ethylenediamine (EDA)과 o-phenylenediamine (o-PDA)을 2-(4-methylthio benzenesulfonyl)-1,3-dimethyl/1-methyl-3-phenyl/1,3-diphenyl/1-methyl-3-ethoxypropane-1,3-dione 3a-d과의 헤테로고리화 반응을 통하여 좋은 생리활성을 나타내는 1H-1,4-diazepines 4a-d과 3H-1,5-benzodiazepines 5a-d을 좋은 수율로 합성하였다. 이 반응에서 ${\beta}$-diketones/${\beta}$-ketoesters 3a-d는 4-methylthiobenzenesulfonyl chloride 1과 다양한 ${\beta}$-diketones/${\beta}$-ketoesters 2a-d과의 축합반응으로 합성하였으며, 합성한 4a-d와 5a-d 화합물들에 대해서 fantimicrobial, antifungal 및 anthelmintic 활성을 측정하였다.

• 약학회지
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• 제57권2호
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• pp.101-109
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• 2013

Depressive disorders are the most common psychiatric problem in the elderly. Most depression treatment guidelines emphasize treatment with antidepressant medication and recommend that benzodiazepine use be minimized for limited period, particularly to elderly patients. In order to evaluate appropriate use of antidepressants and benzodiazepine, retrospective review of prescriptions was performed. The study population are older than 65 years who had been newly diagnosed with major depressive disorder in specialty mental health at a community general hospital from January $1^{st}$, 2007 to October $31^{th}$, 2012 (N=373). Initial antidepressant accounted for 89.5% with SSRI, and escitalopram accounted for 60.9% of SSRI group. 79% or more of the patients were prescribed the recommended dosage. The maintenance rate for 4 weeks of initial antidepressant was 48% and 6 weeks was 39%. Treatment-discontinuation rate was 68% at 3 month. Alprazolam (short acting benzodiazepine) was prescribed the most, followed by clonazepam (long acting benzodiazepine) and then diazepam. 55% of patients received a duplicated prescription for short acting plus long acting benzodiazepine. 61% of patients used long acting benzodiazepines. Prescribed dosages of benzodiazepines were commonly within a recommended range, while no one was prescribed a appropriate period (up to 2 weeks) except for the early discontinued patients. Appropriate use of zolpidem was only 16.2%. The depressed elderly treated in specialty mental health mostly received long-term treatment with benzodiazepines in combination with antidepressants, guideline recommendations was not followed. Multidisciplinary interventions like audit and feedback of benzodiazepine use are needed and education for the elderly is needed to properly maintain antidepressant treatment.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.242-248
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• 1999

Diazepam, a benzodiazepine (BDZ) agonist, produces sedation and flumazenil, a BDZ antagonist, blocks these actions. The aim of this study was to examine the effects of BDZs on cortical electroencephalogram (EEG) in rats. The recording electrodes were implanted over the frontal and parietal cortices bilaterally, and the reference and ground electrodes over cerebellum under ketamine anesthesia. To assess the effects of diazepam and flumazenil, rats were injected with diazepam (1 mgHg, i.p.) and/or flumazenil ( 1 mg/kg, i.p.), and the EEG was recorded before and after drugs. Normal awake had theta peak in the spectrum and low amplitude waves, while normal sleep showed large amplitude of slow waves. The powers of delta, theta and alpha bands were increased during sleep compared with during awake. Diazepam reduced the mobility of the rat and induced sleep with intermittent fast spindles and large amplitude of slow activity, and it produced broad peak over betaL band and increased the power of gamma band, which were different from EEG patterns in normal sleep. Saline injection awakened rats and abolished fast spindles for a short period about 2-5 min from EEG pattern during diazepam-induced sleep. Flumazenil blocked both diazepam-induced sleep and decreased the slow activities of delta, theta, alpha and betaL, but not of gamma activity for about 10 min or more. This study may indicate that decrease in power of betaL and betaH bands can be used as the measure of central action of benzodiazepines, and that the EEG parameters of benzodiazepines have to be measured without control over the behavioral state by experimenter.

• 약학회지
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• 제52권2호
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• pp.137-146
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• 2008

Even though driving under the influence of drug (DUID) is a worldwide problem, we, Korea has no regulation system yet except for alcohol, and there are little cases reported related to DUID. In order to investigate the type of abused drugs for drivers in Korea, we tried to analyze controlled and non-controlled drugs in alcohol-positive blood samples. 275 whole bloods, which were positive for alcohol on the roadside test, were collected from the police for two months ($Nov.{\sim}Dec.$ 2006). The analytical strategy was constituted of three steps: First, alcohol in blood samples were confirmed and quantified by gas chromatography. Second, controlled drugs were screened by $Evidence_{investigator}\;^{TM}$ (Randox, U.K.) as preliminary test. It was based on immunoassay by biochip array analyzer. Nine groups of drug abuse were screened: amphetamines, methamphetamines, cannabis, cocaine, opiates, barbiturates, methadone, benzodiazepines I (oxazepam) & II (lorazepam). Finally, confirmation of these drugs was performed by GC-MS. Blood samples were extracted by solid-phase extraction by $RapidTrace^{TM}$ (Zymark, U.S.A.). After trimethylsilyl (TMS) derivatization, eluates were analyzed to GC-MS. Total 49 drugs were investigated in this study including controlled drugs, antidepressants, 1st generation antihistamines, dextromethorphan, nalbuphine, ketamine, etc. For rapid detection, we developed the automated identification system. It was made up a new software, "DrugMan", modified Chemstation data analysis menu and newly developed macro modules. A series of peak selection, identification and reporting of the results were performed automatically by this system. Concentrations of alcohol in 275 blood samples were ranged from 0.011 to 0.249% (average, 0.119%). Among 149 blood samples, just six samples (4.0%) were showed positive results to the immunoassay: one methamphetamine and five benzodiazepines group I. By GC-MS confirmation, only benzodiazepines were detected and methamphetamine was not detected from immunoassay positive blood sample. Besides these drugs, 5 chlorpheniramines, dextromethorphan, diazepam, doxylamine, ibuprofen, lidocaine and topiramate were also detected in whole bloods by GC-MS. Conclusively, the frequency of drug abuse for Korean drivers was relatively low. There was none case which illegal drug was detected. However these results were limited to alcohol positive blood samples, so it is necessary to analyze more samples including alcohol negative blood.

• Bulletin of the Korean Chemical Society
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• 제24권2호
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• pp.189-192
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• 2003

The reaction of 4-(2-methylaziridin-1-yl)-3-ureidobenzotrifluorides 4 with triphenylphosphine, carbon tetrachloride, and triethylamine (Appel's condition) led to the corresponding carbodiimides 5, which underwent intramolecular cycloaddition reaction with aziridine under the reaction condition to give the benzimidazolefused heterocycles, 2,3-dihydro-1H-imidazo[1,2-a]benzimidazoles 8 and 12,13-dihydro-5H-benzimidazo[2,3-b] [1,3]benzodiazepines 9.

• 대한임상독성학회지
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• 제6권2호
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• pp.91-98
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• 2008

Purpose: The hypnotic effect of zolpidem is comparable to benzodiazepines, but has less abuse and addiction potential than benzodiazepines, so is one of the most commonly prescribed hypnotics. The frequency of acute zolpidem overdose has increased, but clinical analysis and severity predictors are not known in Korea. Methods: A retrospective evaluation of histories, clinical courses, and laboratory findings of each patient treated from June, 2000, to May, 2006, in a university hospital for acute zolpidem intoxication. Results: We evaluated 30 patients, including 16 co-intoxication cases. Twenty-five patients presented mental alterations but became alert within 2 days. All patients recovered completely. The median zolpidem concentration was 0.9 mg/L (range: $0.2{\sim}7.4\;mg/L$). There was a weak correlation between the amount ingested and zolpidem concentration (r=0.25). None of them presented severe laboratory abnormalities, and these abnormalities did not relate to zolpidem concentration. Conclusion: The clinical progress of acute zolpidem intoxication is mild. We could not predict zolpidem concentration or clinical severity from the amount ingested and could not predict the clinical course from laboratory findings in the emergency department.

• 대한임상독성학회지
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• 제12권2호
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• pp.54-62
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• 2014

Purpose: The purpose of this study was to compare prescription patterns and clinical features according to clinical departments in sedative-hypnotic intoxication. Methods: This was a retrospective study of histories, substances of poisoning, acquisition routes, clinical courses, and outcomes of patients treated for acute intoxication in a single emergency medical center from January, 2011 to December, 2013. Results: A total of 769 patients were treated for acute intoxication, 281 patients ingested sedative hypnotics during the study period. Among 281 patients, 155 patients were prescribed by psychiatric department and 80 patients were prescribed by non-psychiatric department. Benzodiazepines were more likely to be prescribed by psychiatrists, and zolpidem was preferred by non-psychiatrists (p<0.001). Non-psychiatrists were more likely to prescribe short acting benzodiazepines than psychiatrists (p<0.001). However, there was no statistically significant difference in the clinical outcomes, including prevalence of admission to ICU, ventilator care, and length of stay in ICU. In patients prescribed by non-psychiatrists, there were more patients prescribed without psychiatric diagnosis and diagnosed as major depression disorder after hospitalization. Conclusion: To promote rational prescribing of sedative hypnotics, proper psychiatric evaluation should be performed before prescribing, and educational programs including the contents of interactions and side effects of sedative hypnotics are needed.

• 대한불안의학회지
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• 제2권1호
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• pp.17-21
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• 2006

SSRIs have been considered as the first line of treatment for patients with panic disorder since 1990s along with cognitive behavioral treatments. High potency benzodiazepines (e.g. alprazolam, clonazepam) have had advantages in anti-panic effects. However, these drugs have limitations of treating panic disorder because of their dependency, tolerance and withdrawal. Serotonin and noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine were introduced as antidepressants since 1990s. Recently, it is confirmed that SNRIs have the remarkable anti-panic effects although some concerns about its cost, tolerance, withdrawal, side effects such as dry mouth, constipation, and hypertension have emerged. In this regard, further study is required to confirm the efficacy of long term treatment of panic disorder. Despite these concerns, venla-faxine extended-release is an effective treatment in patients with panic disorder.

• Journal of Dental Anesthesia and Pain Medicine
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• 제20권1호
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• pp.1-8
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• 2020

Behaviour management and dental procedures performed in very young, pre-cooperative, highly anxious, or medically disabled children are challenging tasks. Various drugs and methods have, however, been introduced to facilitate treatment for this patient population. Midazolam is a benzodiazepine used as an adjunct to behavior management techniques in the dental treatment of pediatric patients. Midazolam can be used as a safe and effective drug for conscious sedation, general anesthetic premedication, and treatment of seizures during dental procedures. Nevertheless, further research involving pediatric patients would be beneficial.