PubMed · 6138024
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J McEwen. 1983. Benzodiazepine dependence.. https://pubmed.ncbi.nlm.nih.gov/6138024/
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The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Linköping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups; medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomitant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries.
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Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine receptors and is widely used as an anaesthetic. Recently, it has been suggested that benzodiazepines modulate cytokine responses. The purpose of the present study was to evaluate the effect of midazolam on interleukin-6 (IL-6) response by observing mRNA expression levels in human peripheral blood mononuclear cells (PBMCs) in the absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers in endotoxin-free 0.9% sodium chloride solution. The cells were incubated for 2 h at 37 degrees C immediately after isolation. IL-6 mRNA expression levels in the cells were quantified using reverse transcription and competitive polymerase chain reaction. It was found that midazolam time-dependently inhibited the IL-6 mRNA expression in PBMCs in the absence of LPS, and significantly inhibited the IL-6 mRNA expression at 1 microg/ml (P<0.05) or 10 microg/ml (P<0.01) in the absence of LPS. However, neither a specific agonist of peripheral-type benzodiazepine receptors, Ro5-4864, nor a specific agonist of central-type benzodiazepine receptors, clonazepam, inhibited IL-6 mRNA expression. These findings indicated a suppression of the IL-6 response in human PBMCs by midazolam in the absence of LPS, and suggests that midazolam has its effect not via benzodiazepine receptors, but by another mechanism.