• 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.

• The Journal of Korean Medicine
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• v.21 no.4
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• pp.271-275
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• 2000

A growing number of people are concerned about their sleep. There are many people with chronic sleep disorders. As there are various causes in a disease, proper treatment according to each cause is necessary for a more effective treatment. In general, insomnia is classified into five categories of physical, physiological, psychological, psychiatric and pharmacological aspects. Sedative-hypnotics including benzodiazepine and non-benzodiazepine have widely been used in chronic insomniacs. However, most hypnotics including non-benzodiazepine cause some of dependence, tolerance, impaired daytime function and rebound insomnia. Therefore, we are looking forward to proposing an effective oriental treatment for insomnia. A 71-year-old male who had suffered from cerebral infarction was admitted to our department for oriental treatment of stroke and insomnia. Initial treatment modalities with administration of paroxetine were not effective. However administration of oriental medicine' Gochimmuwoo-san(Gaozhenwuyou-san)' achieved a desirable effect.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.333-341
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• 2021

Benzodiazepines (BDZs) drugs act on the GABA_A receptor, function as nerve suppressors, and are used to treat anxiety, insomnia, and panic disorder. We analyzed the data of 30 individuals to determine any differences in the sleep-electroencephalogram findings among individuals varying in age, benzodiazepine use, and duration of benzodiazepine use. Comparisons between users and non-users of benzodiazepines, short-term and long-term users, older and younger users, and older short-term and older long-term users, were achieved using electroencephalographic findings obtained through polysomnography. The parameters evaluated included sleep latency, sleep efficiency, sleep-stage percentages, number of sleep spindles, and average frequency of sleep-spindle. The difference between benzodiazepine users and non-users was significant with respect to sleep-stage percentages and average frequency of sleep-spindle. Older and younger users differed significantly with respect to sleep efficiency and sleep-stage percentages, whereas significant difference for sleep efficiency was obtained between long-term and short-term users. Taken together, our results indicate that BDZ consumption suppresses slow-wave sleep and increases the frequency of sleep spindles.

• Archives of Pharmacal Research
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• v.23 no.1
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• pp.31-34
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• 2000

An efficient procedure for the preparation of 7,8-dichloro-6-nitro-1H-1,5-benzodiazepine-2,4-(3H, 5H)-dione(7) as a potential lead compound for the NMDA receptor glycine binding site antagonist, starting from readily available 4,5-dichloro-2-nitroaniline(8), is described. The key step in the synthesis involves the cyclization of malonic ester amide 10 to compound 11.

• Bulletin of the Korean Chemical Society
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• v.28 no.10
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• pp.1877-1880
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• 2007

• Bulletin of the Korean Chemical Society
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• v.32 no.4
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• pp.1179-1182
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• 2011

In the present work, successful implementation of ultrasound irradiations for the rapid synthesis of 1,5-benzodiazepine derivatives under solvent-free conditions is demonstrated. Use of a novel catalyst i.e. camphor sulphonic acid in combination with ultrasound technique is reported for the first time. Comparative study for the synthesis of 1,5-benzodiazepines using conventional as well as ultrasonication method is discussed.

• Archives of Pharmacal Research
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• v.5 no.1
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• pp.27-31
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• 1982

Thank you for inviting me as a guest speaker to this 30th anniversary of the Pharmaceutical Society of Korea. I take it as a compliment to may firm F. Hoffmann-La Roche and Co., Which, has not only dicovered and introduced the benzodiazepines, but has since then been continually in the fore-front of this research. As may subject is going to be "Current Trends in Benzodiazepine Research" I will try to have a look into pending problems. The history of the benzodiazepines has been told several times (e. g. Sternbach, Haefely).

• Journal of The Korean Society of Clinical Toxicology
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• v.14 no.1
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• pp.26-32
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• 2016

Purpose: Aspiration pneumonia is an important complication of drug intoxication with decreased mental status. The purpose of the study is to investigate the risk factors of aspiration pneumonia in the patients of benzodiazepine overdose with or without co-ingestion of other drugs. Methods: A retrospective chart review of patients who visited the emergency department between January 2012 and December 2014 was conducted. Demographic data, time from ingestion to visit, initial vital signs, symptoms, mental status, medical history, laboratory results, chest radiological findings and co-ingested medications were recorded. Multiple logistic analyses were performed to verify the association between variables and the development of aspiration pneumonia. Results: A total of 249 patients presented to the emergency department with benzodiazepine overdose. Aspiration pneumonia had developed in 24 patients (9.6%). Univariate analysis revealed time from ingestion to visit was longer, Glasgow coma scale score was lower, hypoxia was presented, leukocytosis was shown, types of ingested drugs was high, less activated charcoal was applied and tricyclic antidepressants was taken in patients that developed aspiration pneumonia. Time from ingestion to visit (odds ratio (OR) 1.121, 95% confidence interval (CI), 1.057-1.189, p=0.000), GCS score (OR 0.724. 95% CI, 0.624-0.839, p=0.000), oxygen saturation (OR 0.895, 95% CI, 0.835-0.959, p=0.002), and co-ingestion of TCA (OR 4.595, 95% CI, 1.169-18.063, p=0.029) were identified as risk factors of morbidity of aspiration pneumonia upon multiple logistic regression analysis. Conclusion: Time from ingestion to visit, low GCS score, low oxygen saturation and co-ingestion of TCA were risk factors of the development of aspiration pneumonia in benzodiazepine overdose patients.

• 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.

• Natural Product Sciences
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• v.15 no.3
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• pp.130-133
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• 2009

The crude extract of the mycelium of Cladosporium was found to exhibit antimicrobial activity against the Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. Bioassayguided fractionation of an organic extract led to the isolation of an acetophenone derivative, clavatol (2',4'-dihydroxy-3',5'-dimethylacetophenone) (1), and a benzodiazepine alkaloid, circumdatin A (2). Compound 1 showed moderate antibacterial activity against S. aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus with minimum inhibitory concentration (MIC) values of 62.5, 62.5, 31.0 $\mu$g/mL, respectively, but compound 2 was inactive. Compounds 1 and 2 exhibited UV-A protection activity with ED$_{50}$ values of 227.0 and 82.0 $\mu$M, respectively, indicating that they were more potent than the positive control, oxybenzone (ED$_{50}$ 350 $\mu$M), a common sunscreen agent.