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Pilot Studies on the Novel Hypothesis that TSPO (Peripheral Benzodiazepine Receptor) Is Involved in Benzodiazepine/“Z-Drug” Physical Dependence and/or Withdrawal
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作者 Cheyenne Moffett katherine j. kost +4 位作者 Austen Thompson joseph V. Pergolizzi jr. Tally M. Largent-Milnes Robert B. Raffa Todd Vanderah 《Pharmacology & Pharmacy》 CAS 2023年第3期72-83,共12页
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
关键词 BENZODIAZEPINE TSPO Rats In Vivo Tests Western-Blot Analysis
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The FDA Mandate to Reassess Benzodiazepines: Alprazolam Induces a Positive Conditioned Place-Preference in Male Rats 被引量:1
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作者 Cheyenne Moffett katherine j. kost +6 位作者 Austen Thompson Michael H. Ossipov joseph V. Pergolizzi junior Sumiyo Umeda-Raffa Robert B. Raffa Tally M. Largent-Milnes Todd Vanderah 《Journal of Biosciences and Medicines》 2021年第3期1-8,共8页
On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated ... On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats. 展开更多
关键词 BENZODIAZEPINES Conditioned Place-Preference ALPRAZOLAM REINFORCEMENT Affective State
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Test of the Popular Benzodiazepine Alprazolam in a Positive Conditioned Place-Preference Model in Female Rats
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作者 Cheyenne Moffett katherine j. kost +6 位作者 Austen Thompson Michael H. Ossipov joseph V. Pergolizzi jr. Sumiyo Umeda-Raffa Robert B. Raffa Tally M. Largent-Milnes Todd Vanderah 《Pharmacology & Pharmacy》 2021年第5期100-108,共9页
<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternativ... <span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">which </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">suggests that the representative benzodiazepine alprazolam induces positive place preference in female rats.</span> 展开更多
关键词 BENZODIAZEPINE Conditioned Placepreference ALPRAZOLAM Female Rats
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