Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite t...Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.展开更多
[Objectives]To establish an acute yunaconitine poisoning rat model with a single oral administration and to determine the contents of yunaconitine in rat tissues by UPLC-MS/MS method,then investigate the distribution ...[Objectives]To establish an acute yunaconitine poisoning rat model with a single oral administration and to determine the contents of yunaconitine in rat tissues by UPLC-MS/MS method,then investigate the distribution of yunaconitine in rats. [Methods]The rats were randomly divided into three groups and were intragastrically administered a single dose of 2. 2,1. 1,and 0. 7 mg/kg of yunaconitine,respectively.The rats were killed 2 h later,the stomach tissue,intestine tissue,liver tissue,pancreas tissue,kidney tissue,lung tissue,spleen tissue,heart tissue,bladder tissue,testis tissue,brain tissue and heart blood samples were collected. The contents of yunaconitine in the biological materials were determined by UPLC-MS/MS method after the biological samples extracted by liquid-liquid extraction. [Results] A rat model of the yunaconitine poisoning was made with a single dose of 1. 1 mg/kg,the concentrations of yunaconitine shown in the organs with the following order: stomach,small intestine,liver,pancreas,kidney,lung,spleen,heart,bladder,testis,heart blood and brain. [Conclusions]Yunaconitine was widely distributed in rats,especially the levels in the stomach,small intestine and liver were the highest. The conclusion is expected to provide a basis for the selection of test materials for the poisoning of Aconitum vilmorinianum Kom.展开更多
目的:探讨枳实挥发油对慢传输型便秘(STC)大鼠的治疗作用及可能的作用机理。方法:应用盐酸吗啡制作STC模型大鼠,采用活性炭悬液推进法测定枳实挥发油干预前后大鼠肠道推进功能,并采用在体结肠肌电测定法测定枳实挥发油干预前后大鼠结肠...目的:探讨枳实挥发油对慢传输型便秘(STC)大鼠的治疗作用及可能的作用机理。方法:应用盐酸吗啡制作STC模型大鼠,采用活性炭悬液推进法测定枳实挥发油干预前后大鼠肠道推进功能,并采用在体结肠肌电测定法测定枳实挥发油干预前后大鼠结肠的肌电活动情况。结果:与模型对照组相比,枳实挥发油组STC大鼠肠道推进率增加(26.33±7.71%vs 19.74±3.94%,P<0.05),结肠慢波振幅减小、频率加快(0.35±0.05vs 0.43±0.05,8.38±0.96 vs 6.02±1.10,P<0.05),振幅及频率变异系数均减小(11.07±1.21 vs 12.27±1.51,16.35±3.25 vs 23.43±3.02,P<0.05)。结论:枳实挥发油可增强STC结肠推进功能,其治疗作用机制之一是纠正STC异常的结肠慢波,为其用于STC的治疗提供了一定的实验学参考。展开更多
文摘Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.
基金Supported by Scientific and Technological Planning Project of Yunnan Province(2013FB118)Innovation Team Project of Kunming Medical University(CXTD201604)Scientific Research Foundation of Yunnan Provincial Department of Education(2017zDX161)
文摘[Objectives]To establish an acute yunaconitine poisoning rat model with a single oral administration and to determine the contents of yunaconitine in rat tissues by UPLC-MS/MS method,then investigate the distribution of yunaconitine in rats. [Methods]The rats were randomly divided into three groups and were intragastrically administered a single dose of 2. 2,1. 1,and 0. 7 mg/kg of yunaconitine,respectively.The rats were killed 2 h later,the stomach tissue,intestine tissue,liver tissue,pancreas tissue,kidney tissue,lung tissue,spleen tissue,heart tissue,bladder tissue,testis tissue,brain tissue and heart blood samples were collected. The contents of yunaconitine in the biological materials were determined by UPLC-MS/MS method after the biological samples extracted by liquid-liquid extraction. [Results] A rat model of the yunaconitine poisoning was made with a single dose of 1. 1 mg/kg,the concentrations of yunaconitine shown in the organs with the following order: stomach,small intestine,liver,pancreas,kidney,lung,spleen,heart,bladder,testis,heart blood and brain. [Conclusions]Yunaconitine was widely distributed in rats,especially the levels in the stomach,small intestine and liver were the highest. The conclusion is expected to provide a basis for the selection of test materials for the poisoning of Aconitum vilmorinianum Kom.
文摘目的:探讨枳实挥发油对慢传输型便秘(STC)大鼠的治疗作用及可能的作用机理。方法:应用盐酸吗啡制作STC模型大鼠,采用活性炭悬液推进法测定枳实挥发油干预前后大鼠肠道推进功能,并采用在体结肠肌电测定法测定枳实挥发油干预前后大鼠结肠的肌电活动情况。结果:与模型对照组相比,枳实挥发油组STC大鼠肠道推进率增加(26.33±7.71%vs 19.74±3.94%,P<0.05),结肠慢波振幅减小、频率加快(0.35±0.05vs 0.43±0.05,8.38±0.96 vs 6.02±1.10,P<0.05),振幅及频率变异系数均减小(11.07±1.21 vs 12.27±1.51,16.35±3.25 vs 23.43±3.02,P<0.05)。结论:枳实挥发油可增强STC结肠推进功能,其治疗作用机制之一是纠正STC异常的结肠慢波,为其用于STC的治疗提供了一定的实验学参考。
