• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.5-18
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• 1999

A growing number of people are concerned about their sleep. There are many people with chronic sleep disorders. Sedativehypnotics including benzodiazepine and non-benzodiazepine have been widely used in chronic insomniacs. It is widely accepted that current hypnotics are efficient in alleviating subjective symptoms of insomnia. Non-benzodiazepine hypnotics include zolpidem, zopiclone, and melatonin. These novel non-benzodiazepine hypnotics that have efficacy comparable to benzodiazepines were developed with more understanding of benzodiazepine receptor pharmacology. Their unique pharmacologic profiles may offer few significant advantages in terms of adverse effects of benzodiazepines. However, most of hypnotics including non-benzodiazepine have some of dependence, tolerance, impaired daytime function and rebound insomnia. Currently, it is accepted that combination therapy with pharmacologic and behavioral intervention is the most effective for chronic insomniacs.

• Journal of The Korean Society of Clinical Toxicology
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• v.6 no.1
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• pp.45-48
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• 2008

A 57-year-old man was transferred to our emergency department with decreased mental status after organophosphate intoxication. He had a four year history of benzodiazepine and hypnotic medication use for chronic insomnia and a depressive mood disorder. He had no previous history of seizures, diabetes mellitus, and hypertension. By hospital day 5, the patient was noted to be awake and to have repetitive jerking movements involving the left upper extremity, and appeared apathetic, depressed and less responsive to external stimuli. A benzodiazepine withdrawal syndrome was subsequently apparent when he developed several generalized tonic clonic seizures and status epilepticus. Using a continuous midazolam intravenous infusion, we successfully controlled the refractory seizure without complications. We present a rare case of status epilepticus from a benzodiazepine withdrawal that developed during the treatment for organophosphate intoxication.

• 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.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.496-505
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• 1992

The correlation between GABA receptors($GABA_A$ and $GABA_B$ receptor) and benzodiazepine receptor on the saline infusion-induced micturition reflex contraction was studied in the female rat. To investigate the effect of ${\gamma}-aminobutyric$ acid(GABA) on the micturition reflex, exogenous GABA(10 mg/kg) and GABA transaminase inhibitor(aminooxyacetic acid; AOAA $1\;{\mu}g$) were administered intravenously(i.v.) and intracerebroventriculary(i.c.v.), respectively. In result, both GABA and AOAA inhibited the saline induced micturition reflex contraction. This AOAA induced inhibition of micturition reflex was blocked by both bicuculine. $GABA_A$ receptor antagonist, and Ro 15-1788, benzodiazepine receptor antagonist. Muscimol, $GABA_A$ receptor antagonist($0.1\;{\mu}g$ i.c.v., $3\;{\mu}g$ intrathecal; i.t., 1 mg/kg i.v.) and baclofen, $GABA_A$ receptor agonist($1\;{\mu}g$ i.c.v., $3\;{\mu}g$ i.t., 1 mg/kg i.v.) also inhibited the bladder contraction. Pretreatment of bicuculline($1\;{\mu}g$ i.c.v.), but not of 5-aminovaleric acid(AVA, $1\;{\mu}g$ i.c.v.), $GABA_B$ receptor antagonist blocked the central inhibition of muscimol. These inhibitory effects were reversed by Ro15-1788 but were potentiated by flurazepam, benzodiazepine receptor antagonist. On the other hand, the inhibitory effects of baclofen were not affected by Ro 15-1788. Diazepam and flurazepam also inhibited the micturition reflex contraction when they were administered $3\;{\mu}g$ i.c.v., $10\;{\mu}g$ i.t., $10\;{\mu}M$, $30\;{\mu}M$ transurethrally, respectively. In conclusion, these results suggest that the micturition reflex is mediated by $GABA_A$, $GABA_B$ receptor and benzodiazepine receptor. The bezodiazepines increase the receptor binding of GABA to the $GABA_A$ receptor, so that the benzodiiazepines show the synergistic effect on the inhibition of the micturition reflex contraction, but not to the $GABA_B$ receptor.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.238-242
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• 2005

Many reports demonstrate that extremely low frequency magnetic fields (ELF MFs, 60 Hz) may be involved in hyperalgesia. In a previous investigation, we suggested that MFs may produce hyperalgesia and such a response may be regulated by the benzodiazepine system. In order to further confirm this effect of MFs, we used diazepam and/or flumazenil with MFs exposure. When testing the pain threshold of rats using hot plate tests, MFs or diazepam ($0.5\;{\mu}g$, i.c.v.; a benzodiazepine receptor agonist) induced hyperalgesic effects with the reduction of latency. These effects were blocked by a pretreatment of flumazenil (1.5 mg/kg, i.p.; a benzodiazepine receptor antagonist). When the rats were exposed simultaneously to MFs and diazepam, the latency tended to decrease without statistical significance. The induction of hyperalgesia by co-exposure to MFs and diazepam was also blocked by flumazenil. However, the pretreatment of GABA receptor antagonists such as bicuculline ($0.1\;{\mu}g$, i.c.v.; a $GABA_A$ antagonist) or phaclofen ($10\;{\mu}g$, i.c.v.; a $GABA_B$ antagonist) did not antagonize the hyperalgesic effect of MFs. These results suggest that the benzodiazepine system may be involved in MFs-induced hyperalgesia.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.77-86
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• 2004

Objective : This study was performed to investigate the agonistic activity of Chunmajeongal-tang extract to the $GABA_A/benzodiazepine$ receptor complex. Methods : Male mice and Sprague-Dawley rats were used for this experiment. Chunmajeongal-tang Prescription was extracted with 80% methanol, evaporated in vacuo and dried with freeze dryer. The agonistic activity to the GABA/ benzodiazepine receptor complex and GABA transaminase activity were measured in vitro. Results : Chunmajeongal-tang extract inhibited dose-dependently the binding of [3H]Ro15-1788, an antagonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $82.4{\pm}4.12%$ inhibition at a dose of 5.0 mg/kg. This extract inhibited dose-dependently the binding of [3H]flunitrazepam, an agonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $5.6{\pm}1.24%$ inhibition. Furthermore, Chunmajeongal-tang extract inhibited the binding of [3H]flunitrazepam in the presence of GABA/NaCI with $13.2{\pm}0.44%$ inhibition, its inhibitory effect exhibited a positive GABA shift, which means that this extract activates a GABAergic neurotransmission.

• 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.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.

• 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

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.20-26
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• 1999

Purpose : Several modulatory factors for renal peripheral benzodiazepine receptor (PBR) has been reported, but their physiological significance remains elusive. Tissue-specific, stress-induced down-regulation of renal PBR coupled with the pharmacological stimulation of these effects by angiotensin II suggested that physiological significance of renal PBR may be related to the pathophysiology of stress-induced hypertension. The boderline hypertensive rat (BHR) has been used extensively to study the interaction of environmental factors, such as stress and blood pressure. The BHR is the first-generation progeny of a cross between the spontaneously hypertensive rat and the control Wistar-Kyoto rat. The pathogenesis of stress induced hypertension in this model is not demonstrated well. Methods In this study, BHR (male, 150-200 g) and Sprague-Dawley (SD, male, 150-200 g) rats were treated by repeated immobilization to induce anxiety. We used plus-maze performance to observe the level of anxiety by measuring percent open crosses and percent time in open. Results : Percent open crosses and percent time in open in BHR were lower than in SD rats (P<0.05). Receptor densities of renal PBR in BHRs were significantly lower than those of SDs (P<0.05). We also observed that the renal PBR was upregulated in the repeatedly stressed (immobilization, 2 hours daily, for 2 weeks) rats, both in the BHR and SD. However, the density of renal PBR in the stressed BHR was still lower than that of stressed SD. Renal PBR has been suggested to be an important organs which Is responsible for the production of cholesterol-derived products during stress. Conrlusion : From these results, it can be summarized that the lowed density of renal PBR may be involved in the pathogeneis of stress-induced hypertension.