• 수면정신생리
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• 제19권1호
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• pp.18-21
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• 2012

Parasomnias induced by hypnosedatives are rare but serious side effect. Such parasomnias have not been reported with all hypnosedatives. However, frequent use of hypnosedatives, particularly nonbenzodiazepine receptor agonists is associated with parasomnias. Associated symptoms are sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping etc. Mechanisms include high affinity for $GABA_A$ receptor, interruption of the consolidation phase of memory formation by drug, pharmacokinetic or pharmacodynamic drug-drug interaction and concomitant administration with alcohol. Managements for parasomnias induced by hypnosedatives involve stopping medication, switch to other medications or nonpharmacological treatment, lowest effective dose of NBRAs (Non-Benzodiazepine Receptor Agonists), taking into consideration drug-drug interactions, identification and treatment of underlying disease states.

• 대한임상검사과학회지
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• 제53권4호
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• pp.333-341
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• 2021

벤조디아제핀은 GABA_A 수용체에 작용하고 신경 억제제로 작용하며 불안, 불면증 및 공황 장애를 치료하는 데 사용되는 약물 그룹이다. 우리는 연령, 벤조디아제핀 사용 여부 및 사용 기간에 따라 수면 중 뇌파 소견에 차이가 있는지 관찰하기 위해 30명의 개인의 데이터를 분석했다. 수면다원검사를 통해 얻은 뇌파 소견을 이용하여 벤조디아제핀 복용군과 비복용군, 단기 및 장기복용, 노인과 비 노인군, 고령 단기복용 및 고령 장기복용군을 비교했다. 평가된 항목은 수면 잠복기, 수면 효율, 수면 단계별 백분율, sleep spindle의 개수 및 평균 주파수로 설정하였다. 복용군과 비복용군의 비교에서 sleep stage와 sleep spindle의 평균 주파수 항목에서 유의미하였다. 장기복용과 단기복용군의 비교에서 sleep efficiency 항목에서 유의미하였다. 노인군과 비 노인군과의 비교에서 sleep efficiency, sleep stage 항목에서 유의미하였다. 전반적으로 이 연구 결과를 바탕으로 벤조디아제핀의 사용은 느린 주파수 수면을 억제하고 수면 방추파의 주파수와 빈도를 증가시킨다는 결론을 내릴 수 있다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].

• 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.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.586-592
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• 2017

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via ${\gamma}$-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through $GABA_A$-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

• Journal of Ginseng Research
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• 제31권4호
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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.

• 생물정신의학
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• 제8권1호
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• pp.3-19
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• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

• 한국식품영양과학회지
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• 제26권1호
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• pp.37-44
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• 1997

본 실험은 시중에서 판매하는 소시지를 전자렌지(micro-waving), 가스오븐(gas-broiling), 튀김 (frying)으로 조리한 다음, 냉장.저장하였다가 3일째, 6일째에 각 각 재가열하여 관능검사와 조직감 측정을 하였다. 이를 통하여 조리 방법, 냉장.저장 후 재가열에 따른 조직 특성에 대해 연구하여 다음과 같은 결론을 보고하는 바이다. 관능검사결과를 조리 방법 별로 살펴보면 조리 하지 않은 상태의 소시지가 촉촉한 정도, 경도에서 높은 수치를 나타내었으며, 짠맛의 정도는 재가열함에 따라 수치가 높아졌다. 저작성은 전자렌지 조리에서 높은 수치를 보였으나 두 제조회사 제품이 다른 양상을 보였다. 뒷맛은 가스오븐 조리에서 가장 높게 나타났고, 조리하지 않은 상태의 소시지가 뒷맛이 가장 약함을 보였다. 산패취는 다른 조리방법에 비하여 튀김 조리에서 유의하게 높게 나타났다. 조리하여 냉장 저장 한 후 3일째, 6일째 재가열했을 때, 저장 기간이 길어짐 에 따라 경도, 짠맛의 정도, 산패취, 뒷맛의 수치는 증가함을 보였으나 촉촉한 정도, 저작성은 감소함을 보였다. 전반적인 기호도는 전자렌지와 가스오븐으로 조리하여 냉장.저장한 후 3일째 재가열했을 때가 가장 높은 수치를 나타내었다. 기계적인 분석을 하였을 때 튀김조리에서 경도, 뭉침성, 씹힘성이 높은 수치를 나타냈으며, 응집성과 탄력성에서는 조리방법 별로 유의한 차이는 나타내지 않았다. 조리하여 냉장.저장한 후 재가열할 때에는 3일째, 6일째 재가열할수록 경도, 응집성, 탄력성, 뭉침성, 씹힘성이 증가하는 경향을 보였다. 경도, 응집성, 뭉침성, 씹힘성은 가스오븐으로 조리하여 냉장 저장한 후 3일째에 재가열한 소시지에서 유의하게 높았다.우(각각 20.0%), 땅콩 및 콩(각각 16.7%) 등의 순이었다. 연령 대별로는 10대 이하에서는 우유, 20대~30대에서는 복숭아, 40대 이상에서는 돼지고기가 많이 나타났다.ing of [sub 3/H]SR95531 to GABA receptor. Butanol fraction of G. elata significantly diminished the pentylenetetrazole-induced lethality of mice. From these results, it can be concluded that substance or substances with neurochemical properties characteri- stic of a benzodiazepine receptor agonist may be important components, and contribute to the anticonvulsant property of G. elata.clooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is