1.Clinical Evaluation of Flunitrazepam as a Preanesthetic Medicant .
II Young KWAK ; Yong Lack KIM ; Kwang Won YUM
Korean Journal of Anesthesiology 1973;6(1):23-29
No abstract available in English.
Flunitrazepam*
2.Superfluous Use of Benzodiazepines in Patients with Major Depression Treated with Mirtazapine.
Ho Suk SUH ; Chan Hyung KIM ; Min Seong KOO ; Hong Shick LEE
Korean Journal of Psychopharmacology 2004;15(1):58-65
OBJECTIVE: The purpose of this study is to evaluate the usefulness of administration of benzodiazepines in patients with major depression being treated with the antidepressant mirtazapine. METHODS: The subjects of this study included 503 patients between 18 and 65 years of age. They were diagnosed with major depression according to the ICD-10 and scored over 18 at baseline on the 17-item HAM-D scale. They were among the 925 patients who have participated in the Remeron (mirtazapine) post-marketing surveillance carried out between September 1999 and December 2000 at 33 institutes in Korea. The patients were initially started on 15 mg/day or 30 mg/day of mirtazapine orally and the dosages could be changed according to clinical judgment during the trial. Benzodiazepines could also be administrated according to clinical judgment. The clinical effects were evaluated before and 1, 2 and 6 weeks after treatment initiation. The therapeutic action of mirtazapine was evaluated using the 17-item HAM-D and CGI. The adverse effects were rated according to patient reports. RESULTS: Their mean age was 45 years old and 61.6% were women. 391 subjects (77.3%) from a total of 503 patients completed the trials. 313 (62.2%) patients were administrated benzodiazepines during the trial. These were alprazolam 37.0%, lorazepam 12.5%, clonazepam 9.1% and diazepam 7.0%. The reasons for prescribing benzodiazepines were: anxiety 43.1%, insomnia 18.3% and somatic symptoms 3.8%. The HAM-D scores of total patients were reduced from 26.1 to 10.9, and CGI scores from 4.5 to 3.0 after 6 weeks with significant changes beginning after 1 week of treatment. No significant differences were found in terms of each interval changes on the HAM-D and CGI scores between the groups with and without benzodiazepines. There were no significant differences of each interval changes of anxiety/agitation factors and sleep disturbance factors between the two groups. The occurrence of side effects was not significantly different between the two groups. CONCLUSION: Administration of benzodiazepines in patients with major depression being treated with mirtazapine may not be useful in reducing depressive symptoms, even for anxiety/agitation and sleep disturbance symptoms.
Academies and Institutes
;
Alprazolam
;
Anxiety
;
Benzodiazepines*
;
Clonazepam
;
Depression*
;
Diazepam
;
Female
;
Humans
;
International Classification of Diseases
;
Judgment
;
Korea
;
Lorazepam
;
Middle Aged
;
Sleep Initiation and Maintenance Disorders
3.Superfluous Use of Benzodiazepines in Patients with Major Depression Treated with Mirtazapine.
Ho Suk SUH ; Chan Hyung KIM ; Min Seong KOO ; Hong Shick LEE
Korean Journal of Psychopharmacology 2004;15(1):58-65
OBJECTIVE: The purpose of this study is to evaluate the usefulness of administration of benzodiazepines in patients with major depression being treated with the antidepressant mirtazapine. METHODS: The subjects of this study included 503 patients between 18 and 65 years of age. They were diagnosed with major depression according to the ICD-10 and scored over 18 at baseline on the 17-item HAM-D scale. They were among the 925 patients who have participated in the Remeron (mirtazapine) post-marketing surveillance carried out between September 1999 and December 2000 at 33 institutes in Korea. The patients were initially started on 15 mg/day or 30 mg/day of mirtazapine orally and the dosages could be changed according to clinical judgment during the trial. Benzodiazepines could also be administrated according to clinical judgment. The clinical effects were evaluated before and 1, 2 and 6 weeks after treatment initiation. The therapeutic action of mirtazapine was evaluated using the 17-item HAM-D and CGI. The adverse effects were rated according to patient reports. RESULTS: Their mean age was 45 years old and 61.6% were women. 391 subjects (77.3%) from a total of 503 patients completed the trials. 313 (62.2%) patients were administrated benzodiazepines during the trial. These were alprazolam 37.0%, lorazepam 12.5%, clonazepam 9.1% and diazepam 7.0%. The reasons for prescribing benzodiazepines were: anxiety 43.1%, insomnia 18.3% and somatic symptoms 3.8%. The HAM-D scores of total patients were reduced from 26.1 to 10.9, and CGI scores from 4.5 to 3.0 after 6 weeks with significant changes beginning after 1 week of treatment. No significant differences were found in terms of each interval changes on the HAM-D and CGI scores between the groups with and without benzodiazepines. There were no significant differences of each interval changes of anxiety/agitation factors and sleep disturbance factors between the two groups. The occurrence of side effects was not significantly different between the two groups. CONCLUSION: Administration of benzodiazepines in patients with major depression being treated with mirtazapine may not be useful in reducing depressive symptoms, even for anxiety/agitation and sleep disturbance symptoms.
Academies and Institutes
;
Alprazolam
;
Anxiety
;
Benzodiazepines*
;
Clonazepam
;
Depression*
;
Diazepam
;
Female
;
Humans
;
International Classification of Diseases
;
Judgment
;
Korea
;
Lorazepam
;
Middle Aged
;
Sleep Initiation and Maintenance Disorders
4.Identification of New Designer Benzodiazepine Diclazepam in Drug Facilitated Sexual Assault.
Ping XIANG ; Bao Hua SHEN ; Hui YAN ; Wei LIU ; Min SHEN ; He Jian WU ; Xiana Yi ZHUO
Journal of Forensic Medicine 2018;34(3):248-252
OBJECTIVES:
To identify the new designer drugs which are totally unknown and not in the routine testing list by the technologies such as high-resolution mass spectrometry in drug facilitated sexual assault, in order to solve the problem in actual cases.
METHODS:
The milky fluid from an actual case was extracted and analyzed using LC-QE, ¹H-NMR and GC-MS, respectively. The accurate masses and cluster ions isotope patterns of unknown compound were obtained by LC-QE. The molecular formula was confirmed as C₁₆H₁₂C₂N₂O based on the protons number of ¹H-NMR. The isomers diclazepam and 4-chlorodiazepam were separated and detected with GC-MS.
RESULTS:
The new designer benzodiazepine as diclazepam in the milky fluid was identified. The results provided direct evidence for the investigation and qualitative analysis of such cases.
CONCLUSIONS
The combined application of various methods, including LC-QE, ¹H-NMR and GC-MS, can be used to detect unknown new psychoactive substances.
Benzodiazepines/chemistry*
;
Benzodiazepinones
;
Chromatography, Liquid/methods*
;
Designer Drugs/chemistry*
;
Female
;
Gas Chromatography-Mass Spectrometry/methods*
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Humans
;
Male
;
Mass Spectrometry/methods*
;
Sex Offenses
;
Substance Abuse Detection/methods*
;
Toxicology/methods*
6.Reverse Effect of Flumazenil on the Cerebral and Circulatory Functions Suppressed by Lorazepam in Dogs .
Yong Seok OH ; Young Chon WON ; Yong Lak KIM
Korean Journal of Anesthesiology 1991;24(5):916-924
The effects of lorazepam on cerebral function, metabolism, and hemodynamics were studied in eight dogs receiving a general anesthesia with isoflurane(0.5 vo1%)-50% nitrous oxide-oxy-gen. The effects of benzodiazepine antaronist, flumazenil, were also examined. Lorazepam(0.5 mg/kg) administration did decrease mean arterial pressure(MAP) and herat rate(HR). It did significantly decrease cerebral blood flow(CBF)(measured by posterior sagittal sinus outflow method) by 25% of control value(68+/-l3 vs. 51+/-12ml/100gm/min, meanSD) and cereberal metabolic rate for oxygen(CMRO ) by 17% (3.96+/-1.04 vs. 3.30+/-0.92ml/l00gm/min, mean+/-SD). Electroencephalogram(EEG) converted to high amplitude, predominantly theta and delta activity. Intracranial pressure(ICP) increased markedly. Following flumazenil(0.06 mg/kg) administration, HR recovered completely to control level but MAP increased only at 5 min. compared to pre-flumazenil value and returned to pre-flumazenil level. CBF recovered to control level for 15 min. and deereased after 30 min. compared to control level but higher than pre-flumazenil level about 9-15%. CMRO recovered completely to control leveL EEG changed to an awake pattern after fluamzenil administration. It is concluded that lorarepam decreased cerebral function and metabolism and depressed hemodynamic fuction. Benzodiazepine antag- onist, flumazenil, was effective in reversing cerebral and hemodynamic effects, may be in dose related manner.
Anesthesia, General
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Animals
;
Benzodiazepines
;
Dogs*
;
Electroencephalography
;
Flumazenil*
;
Hemodynamics
;
Lorazepam*
;
Metabolism
7.Evaluation of Flunitrazepam ( Rohypnol ) as a Preanesthetic Medicant for Small Children .
Koo Young CHUNG ; Woon Hyok CHUNG
Korean Journal of Anesthesiology 1978;11(3):191-197
To assess the effect of premedication for pediatric cases, flunitrazepam (Rohypnol) was given to small children under 6 years of age. 70 patients were divided into 4 groups to which the drug was given intramuscularly, 0. 06 mg, 0.1 mg, 0.15 mg and 0. 2 mg per kilogram of body weight, of the drug respectively. The dose was given 30 minutes before anesthesia and the maximum dose was limited to 2.0 mg for each patient if the calculated dose of the drug exceeded this amount. 1) The shortest time of onset of sleep was 5 minutes. The group which fell asleep between 5 and 10 minutes did not respond to needle stimulation. The group which fell asleep between 11 and 15 minutes moved upon needle stimuli but an intravennous needle was inserted without difficulty. 2) The group which fell between 16 and 20 minutes and became sedated after 20 minutes. without asleep was induced by anesthesia with an inhalational agent but aroused by needle stick. The last group was sedated in presence of their guardian only and became uncooperative when they were separated from the latter. 3) The patients were not affected at all with the dose of 0.06mg/kg of flunitrazepam. 4) With the dose of 0. 1 mg/kg, the group under 6 months of age did not sleep and in the; group between 4 and 6 years of age, half did sleep. ) With the dose of 0.15 mg/kg, in the group under the age of one year, 50% of the cases slept and in the group between 2 and 6 years of age, 30% of the cases slept. 6) With the dose of 0. 2 mg/kg, the sleep group was 25% under 1 year of age, 30. 8% between one and 3 years of age and 33% between 4 and 5 years of age, but the maximum. dose given was limited to 2 mg for each case. A tendency to increased effect according to the increase of age was noticed. 7) The optimum dose of the drug was suggested to be 0. 15 mg/kg and if a dose was used of more than 2. 0 mg, it was not needed to increase above this amount for the purpose of sedation. 8) Optimal time for premedication was suggested to be 30 minutes before the induction of anesthesia. 9) Respiratory and circulatory depression were not noticed with the above doses. 10) Endotracheal intuhation was faeilitated without the aid of muscle relaxant in about 30% of cases when 0.15mg)kg Of the drug was given. (Acknowledgement: We are grateful to Roche Far East Research Foundation for supplies of flu- nitrazepam for this study and to Dr. R. Lassere for advice.)
Anesthesia
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Body Weight
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Child*
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Depression
;
Equipment and Supplies
;
Far East
;
Flunitrazepam*
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Humans
;
Needles
;
Nitrazepam
;
Premedication
8.Secretory response of cultured acinar cells of rat pancreas to cholecystokinin.
Yonsei Medical Journal 1996;37(6):405-411
To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acina response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.
Amylases/secretion
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Animal
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Benzodiazepinones/pharmacology
;
Cells, Cultured
;
Cholecystokinin/*pharmacology
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Devazepide
;
Dose-Response Relationship, Drug
;
Hormone Antagonists/pharmacology
;
Lipase/secretion
;
Male
;
Pancreas/cytology/*drug effects/*secretion
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Rats
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Rats, Sprague-Dawley
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Receptors, Cholecystokinin/antagonists & inhibitors
;
Support, Non-U.S. Gov't
9.Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription.
Yan-Boi TANG ; Chuan-Ming ZHANG ; Cheng FANG ; Chun HU ; Li HUANG ; Chin-Ho CHEN ; Zhi-Yan XIAO
Acta Pharmaceutica Sinica 2011;46(6):688-694
HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).
Benzodiazepinones
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chemical synthesis
;
chemistry
;
pharmacology
;
Cell Line, Tumor
;
HIV Long Terminal Repeat
;
genetics
;
HIV-1
;
genetics
;
Humans
;
Transcription, Genetic
;
drug effects
;
tat Gene Products, Human Immunodeficiency Virus
;
antagonists & inhibitors
10.Peripheral benzodiazepine receptor agonist Ro5-4864 inhibits mitochondrial permeability transition in rat heart.
Jing-Yuan LI ; Jun-Ke WANG ; Yin-Ming ZENG
Acta Physiologica Sinica 2007;59(1):13-18
Opening of mitochondrial permeability transition (MPT) pores leads to mitochondrial injury during oxidative stress. The peripheral benzodiazepine receptor (PBR) located at mitochondrial outer-membrane has been shown to be involved in several mitochondrial functions. In the present study, we used Ro5-4864, a PBR agonist, to test if activation of PBR could prevent MPT pore opening during Ca(2+) overloading. Cardiac mitochondria isolated from Sprague-Dawley rats were treated by 150 mmol/L Ca(2+) to induce MPT. Ro5-4864 (50, 100 and 200 micromol/L) was added into incubation buffer before adding 150 micromol/L Ca(2+). In additional group, atractyloside (ATR, 20 micromol/L), an opener of MPT pores was added 5 min before the addition of 100 micromol/L Ro5-4864. The change of absorbance at 520 nm was monitored with a spectrophotometer at 30 degrees C for 10 min. Western blot was used to detect cytochrome C loss. The mitochondrial membrane potential was monitored with the fluorescence dye JC-1. Ro5-4864 inhibited the decrease of absorbance at 520 nm compared to that in the untreated Ca(2+) group (P<0.01, P<0.05). In the presence of ATR, Ro5-4864 was not able to prevent MPT anymore. Opening of MPT pores by Ca(2+) decreased the content of cytochrome C in mitochondria, but increased cytochrome C content in cytosol. Ro5-4864 preserved cytochrome C content in mitochondria and led to less cytochrome C release to cytosol. ATR treatment reversed the protective effect of Ro5-4864 on cytochrome C content. Opening of MPT pores led to mitochondrial depolarization, whereas Ro5-4864 treatment maintained mitochondrial membrane potential. Thus, prevention of MPT by activation of PBR during calcium overloading maintains mitochondrial cytochrome C content and membrane potential. Activation of PBR during cardiac ischemia and reperfusion may be an alternative way for cardioprotection.
Animals
;
Atractyloside
;
pharmacology
;
Benzodiazepinones
;
pharmacology
;
Carrier Proteins
;
agonists
;
metabolism
;
physiology
;
Female
;
Male
;
Membrane Potential, Mitochondrial
;
physiology
;
radiation effects
;
Mitochondria, Heart
;
physiology
;
Mitochondrial Membrane Transport Proteins
;
drug effects
;
physiology
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, GABA-A
;
metabolism
;
physiology