• 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.

• 정신신체의학
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• 제27권2호
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• pp.111-118
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• 2019

연구목적 본 연구에서는 섬망 증상 조절을 위한 항정신병약물 처방에 영향을 주는 임상적 특징을 알아보고자 한다. 방 법 연세대학교 원주세브란스 기독병원에 입원하여 정신건강의학과에 협진 의뢰된 환자 중, 일반신체질환에 의한 섬망으로 진단된 185명을 대상으로 후향적 의무기록을 조사하였다. 항정신병약물을 사용한 군과 사용하지 않은 군으로 구분하여 임상적 특성을 비교 분석하였다. 결 과 항정신병약물 사용군은 129명(66.5%)으로 정신과약물 사용력이 많았다. 특히 벤조디아제핀계 약물 사용력에서 두 군 간에 유의미한 차이를 보였다. 섬망평가척도 대다수에서 항정신병약물 사용군이 높은 점수를 보였다. 결 론 항정신병약물 사용군은 섬망의 외현 증상이 두드러지며 기저에 벤조디아제핀계 약물 복용력이 높았다. 이는 벤조디아제핀이 섬망의 경과와 외현 증상에 영향을 주었을 가능성이 있다. 임상 현장에서 예후에 영향을 줄 수 있는 섬망의 임상적 특징에 대한 이해가 축적되어야 할 것이다.

• 한국임상수의학회지
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• 제27권4호
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• pp.336-342
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• 2010

본 연구는 tiletamine/zolazepam 대조군과 대조군에 benzodiazepine의 길항제인 flumazenil을 투여한 실험군의 마취 효과와 혈액생화학, Vital sign, 마취회복시간에 대하여 비교하였다. 건강한 6마리의 개들(평균 체중 $5.2{\pm}2.2$)이 실험에 이용 되었다. Tiletamine/zolazepam 을 투여하였고 20분 뒤에 benzodiazepine의 길항제인 flumazenil 0.1 mg을 투여하였다. 마취효과 (Sedation, analgesia, muscle relaxation, posture and auditory response score), Vital sign (심박수, 호흡수, 체온), 혈액 생화학 (GLU, TP, ALT, AST) 검사들이 두 그룹에서 tiletamine/zolazepam 투여전, 투여후 1, 5, 20, 30, 60 그리고 90분에 실시되었다. 또한 마취회복시간 (head up, sternal recumbency, standing and walking times)은 부동화 상태에서 각 행동양식 이 보이는 시간까지 측정되었다. Analgesia score는 투여 후 20분과 30분에, posture score는 투여 후 30분에 그리고 auditory response score는 투여 후 1분과 20분에 TZF그룹이 TZ그룹보다 유의하게 낮아 benzodiazepine에 대한 flumazenil의 길항효과를 나타냈다. 평균 심박수는 두 그룹 모두 투여 후 1분부터 급상승하여 유의하게 정상 심박수 보다 높았다. 평균 호흡수는 TZF그룹이 TZ그룹보다 유의하지 않았으나 높은 호흡수를 보였다. 결론적으로 개에서 flumazenil의 투여는 tiletamine/zolazepam에 대한 길항작용을 나타내었다. 마취로 부터의 회복에 있어서, flumazenil은 sternal recumbency, standing 및 walking times를 단축시켰다.

• 핵의학기술
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• 제12권3호
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• pp.176-180
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• 2008

Department of Nuclear Medicine in Seoul National University Hospital (SNUH) had developed $^{18}F$-Flumazenil as Benzodiazepine receptor imaging agent for PET diagnosis of Epilepsy. But production Activity of $^{18}F$-Flumazenil is decreased owing to this method has difficult synthesis procedures and pretty long synthesis time. In this study, we can modify synthesizing method to have more simple procedure and less spend time and help to increase production Activity. Old method: Radioactivity was produced by cyclotron was captured by QMA cartridge that was activated. Captured radioactivity was eluted into the reaction vial by using kryptofix solution and delivered. After evaporation of eluent, the azeotrophic drying step repeated two times. tosylflumazenil in anhydrous Acetonitrile was added to a reaction vial while bubbling. The reaction mixture was evaporated until the mixture volume was 0.5 mL. Reaction vial washed with 20 % Acetonitrile and that solution went into the reaction vial. The reaction mixture was loaded to the HPLC loop by hand and purified $^{18}F$-Flumazenil by HPLC column. New method: We used $TBAHCO_3$ solution as a eluent. After the eluent was evaporated, tosylflumazenil in anhydrous acetonitrile was added to a reaction vial and the reaction mixture was bubbled for 15 minutes. It was evaporated until the mixture volume became 0.5 mL. It was loaded to the HPLC loop. In old method, $^{18}F$-Flumazenil was synthesized via 6 steps synthesis procedures in 105 minutes with 30~35% synthesizing yield (non-decay correction) and specific activity was about $0.5{\sim}2{\times}10^5$ Ci/mole. In new method, It had 3 steps synthesis procedures in 53 minutes with 40~45% synthesizing yield and specific activity was about $3{\sim}8{\times}10^5$ Ci/mole. This method leads to improve of minimizing synthesis time, increasing synthesis yield and specific activity. While we can load reaction mixture to the HPLC loop, we can expose high radiation field thanks to used by hand.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.120-120
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• 2005

• Bulletin of the Korean Chemical Society
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• 제29권11호
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• pp.2135-2139
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• 2008

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.123.2-123.2
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• 2002

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.342.2-342.2
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• 2002

The ${\beta}$-turn has been implicated as an important conformation for biological recognition of peptides or proteins. Benzodiazepine classes have been known as one of the non peptide ${\beta}$-turn mimic scaffolds. We have developed an efficient approach for the synthesis and derivatization of a scaffold of hydroxytetrahydrodizepinone class in order to screen compound library in various protein targets for new lead generations as well as for structure activity relationships of the scaffold. (omitted)

• 대한임상독성학회지
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• 제14권2호
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• pp.92-99
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• 2016

Purpose: The use of flumazenil administration in the emergency department is still controversial because of concerns about adverse effects. The present study was conducted to re-evaluate the risk-benefit ratio associated with flumazenil administration to patients suspected of having acute hypnotics and sedatives poisoning in the emergency department. Methods: A retrospective chart review study was conducted for patients whose final diagnoses were "poisoning" and "benzodiazepine" or "sedatives-hypnotics" from Mar. 2006 to Feb. 2015. The basal characteristics of the patients, including past medical history, ingredients and dose of ingested drug and co-ingested drugs were investigated. For patients administered flumazenil, responsiveness and time from admission to flumazenil administration were investigated with supplement. All collected data were analyzed in aspect terms of risk/benefit. Results: A total of 678 patients were included in our study. Benzodiazepine was the most common sedative/hypnotic drug prescribed, and the frequency of prescription continuously increased. The proportion of TCA as co-ingestion decreased from 13.1% to 3.9% in patients with acute sedative/hypnotic poisoning. Flumazenil was administered to 55 patients (8.1%), of which 29 patients (52.7%) were applied to contraindications. Fifty-three patients (96.4%) showed positive responsiveness, including partial responsiveness after flumazenil administration. No severe adverse events were identified. Conclusion: Based on the current trends in prescription patterns for sedative/hypnotic drugs, increased use of non-TCA antidepressants, and responsiveness to administration of flumazenil, benefit seemed weighted more in this study, although the observed benefits were based on limited results. Further prospective multicenter studies will be needed to optimize benefit-risk ratio.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.555-563
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• 1998

The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 ${\mu}g/kg,$ elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 ${\mu}g/kg$ diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 ${\mu}g/kg$ icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 ${\mu}g/kg$ given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 ${\mu}g/kg$ muscimol was given 3 min prior to 30 ${\mu}g/kg$ of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.