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Central Stress-Limiting Systems and Cardioprotective Effects of their Mediators and Activators
Published in Felix Z. Meerson, Alexander V. Galkin, Adaptive Protection of The Heart: Protecting Against Stress and Ischemic Damage, 2019
Felix Z. Meerson, Alexander V. Galkin
Phenazepam is well known as a psychotropic and anticonvulsive drug. Therefore, we first studied the antiarrhythmic action of phenazepam in the above conditions and then briefly collated the antiarrhythmic and the anticonvulsive properties of this benzodiazepine receptor agonist.
Designer Benzodiazepines
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Peter D. Maskell, Nathan E. Wilson
The abuse of benzodiazepines was recognized quickly after their release onto the market in 1961. Because of their recognized abuse, in 1971, 33 benzodiazepines were placed under control by the UN Convention on Psychotropic Substances. This has risen to 36 recently because of the emergence of NPS benzodiazepines (International Narcotics Control Board (INCB) 2016). Studies into the abuse of benzodiazepines have suggested that they are used to get high, alleviate stress, or help with sleep (Kapil, Green, Le Lait, Wood, & Dargan, 2014); when used with other drugs, such as opioids, benzodiazepines are abused to reduce the withdrawal effects of the opioids and to enhance or prolong the effects of the concomitantly used drug of abuse (Vogel et al., 2013). The source for abused benzodiazepines has changed over time. Before 2007, benzodiazepines were diverted from both legal sources (false prescriptions, pharmacies) and also illicitly manufactured, but the illicit use of benzodiazepines were benzodiazepines that were available for prescription in that country (Ibañez, Levi-Minzi, Rigg, & Mooss, 2013). In 2010, however, the USA (Bailey et al., 2010), and the UK in 2011 (Maskell, De Paoli, Seetohul, & Pounder, 2011), started to detect phenazepam, a drug that was at that time only available for prescribing in the former Soviet states, in drug-related deaths (DRD). Phenazepam as well as nimetazepam were also detected a few years earlier in Europe in 2007 (UNODC 2013) in seizures by customs and law enforcement agencies in Europe, but at the time, there had been no cases of detection in human samples, either clinical or post-mortem. These detections were the start of the rise of what are now termed new psychoactive substances (NPS) (also known as ‘legal highs’, ‘designer drugs’, and ‘bath salts’) throughout the world. This rise of NPS has been particularly prevalent in Europe where the EMCDDA via the European Early Warning System (EU-EWS) is now monitoring over 620 substances, with 20 of these being benzodiazepines (European Monitoring Centre for Drugs and Drug Addiction, 2017). As can be seen in Table 19.1, there has been a small but increasing trend in the detection of ‘new’ benzodiazepines being reported to the EMCDDA each year (European Monitoring Centre for Drugs and Drug Addiction, 2017), leading the UN to consider the nonmedical use of benzodiazepines as a ‘growing threat to public health’ (Lobal, Mart, & En 2017.). The rise of the use of chemical compounds that have physiological and psychological effects but have not been properly tested in clinical trials like licenced medicines is worrying from both a social and medical angle with the drugs having unknown dangers.
Melatonin and alcohol-related disorders
Published in Chronobiology International, 2020
Natalia Kurhaluk, Halyna Tkachenko
The efficacy of Mel in patients with drug addiction as a treatment of alcohol dependence has also been demonstrated. This hypnotic agent in a nightly dose of 6–9 mg was shown to be a better hypnotic than phenazepam prescribed during the period of acute alcohol withdrawal syndrome (Bykov et al. 2016). On the other hand, a positive effect of Mel ingested in a smaller nighttime dose of 3 mg for alcoholic insomnia was shown against the background of remission stabilization (Bykov et al. 2016). Also, the efficacy of Mel as a sleeping pill is dependent on good sleep hygiene practices, as reflected in the instructions for its use. Sleep accompanied in the presence of light noise or light (especially of the blue spectrum) contributes to the destruction of Mel and reduction of its effectiveness (Lemoine et al. 2011). Wade et al. (2011) reported enhancement of the efficacy of Mel as a sleep therapy after 6 months, in comparison to the first month, of use. Moreover, these researchers demonstrated insomnia patients 55 yrs of age and older benefitted the most from the short- and long-term efficacy of prolonged-release melatonin formulation (Wade et al. 2011).
Designer benzodiazepines: a report of exposures recorded in the National Poison Data System, 2014–2017
Published in Clinical Toxicology, 2019
Joseph E. Carpenter, Brian Patrick Murray, Camille Dunkley, Ziad N. Kazzi, Melissa H. Gittinger
Specific assays for several designer benzodiazepines and their metabolites have only recently been described [20–22], contributing to a lack of exposure and mortality data. In one report, the Georgia Bureau of Investigation had to develop their own in-house phenazepam assay to evaluate a cluster of individuals who were observed to be driving while intoxicated [23]. In that cluster, phenazepam was confirmed in biological samples from all 11 cases, however in 6/11 cases at least one additional drug was detected. In three additional case reports from the United States during the study period, liquid chromatography/mass spectroscopy was used to confirm the presence of etizolam, flubromazolam, and clonazolam in biological samples from patients suspected of ingesting a designer benzodiazepine [10,24,25]. Therefore, confirmatory testing has verified the suspected agent in all case reports that we reviewed.
Designer benzodiazepines: an update
Published in Expert Review of Clinical Pharmacology, 2023
Xiao Yu, H Karl Greenblatt, David J Greenblatt
Mortality related to the sole use of DBs is rare. Data collected in South Scotland from 2010 to 2014 reported 228 cases of phenazepam detection in post-mortem blood samples. In only two cases was the cause of death attributed to phenazepam. Fifty-four cases involved drug combinations, and 83 cases detected phenazepam, but this was not the cause of death [21–30]. Blood samples from nine fatal cases detected flualprazolam, but the cases involved multiple drugs, and none of the deaths could be attributed to flualprazolam [31]. Flualprazolam was reported with relatively high frequency in forensic investigation cases both in the United States and in Scandinavian countries [32,33]; mixed drug ingestions accounted for the majority of bad outcomes.