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Designer Benzodiazepines
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Peter D. Maskell, Nathan E. Wilson
The lack of pharmacological testing of the NPS benzodiazepines to date either using functional in vitro or in vivo testing has made it difficult to determine the potency of the NPS benzodiazepines. Quantitative structure activity relationship (QSAR), which relates the structure of the molecules to biological activity using a known model, allows some initial prediction of potency. triazolobenzodiazepines (such as etizolam) are generally more potent than 1,4-benzodiazepines (such as diazepam), although individual potency will depend on the functional groups present (Hester, Duchamp, & Chidester, 1971; Meguro & Kuwada, 1970) and so does not allow more than a rudimentary determination of the potency. Recent work by Waters et al. has developed a QSAR model to determine the biological activity of NPS benzodiazepines (Waters, Manchester, Maskell, Haegeman, & Haider, 2018) that show the strength of binding of the drugs to the GABA-A receptor but not the pharmacological potency. The best current method to develop some idea of the potency of the NPS benzodiazepines is to look at the common dose of NPS benzodiazepines taken by users—the scale being from the most potent drugs (+++++) to the least potent drugs (+) (Table 19.3), with the potency of the individual NPS benzodiazepines shown in Table 19.2. This assumes that the common dose of the drug gives a similar level of effect in an individual, which may not be true. To give an idea of the potency, diazepam would score (+/++), whereas clonazolam, flubromazolam, and flunitrazolam would be the most potent drugs (+++++) correlating with user reports (Huppertz et al., 2018; Anon n.d.; Theis 2017.; Andersson & Kjellgren, 2017). Because of the very low dose (~0.5 mg) that is needed for these drugs, it is possible that the user may easily overdose because of the difficulty in measuring the dose if using the powder form. If taking tablets, as the quality control of the illicit manufacturers is poor, it is highly likely the users will take a dose that they did not intend to. The NPS benzodiazepines are, however, the NPS grouping that have the lowest risk of fatal toxicity of the NPS compounds. This should, however, not be taken as meaning that they are safe compounds to take (King & Corkery, 2018).
Non-fatal intoxications involving the novel benzodiazepine clonazolam: case series from the Emerging Drugs Network of Australia – Victoria project
Published in Clinical Toxicology, 2023
Rebekka Syrjanen, Shaun L. Greene, Jared W. Castle, Matthew Di Rago, Sarah E. Hodgson, Rachelle Abouchedid, Andis Graudins, Jennifer L. Schumann
Clonazolam (6-(2-Chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine) is a triazolo-substituted 1,4-benzodiazepine derived from clonazepam [1]. Clonazolam was first characterised in 1971 [1] but has never been registered for pharmaceutical use. In 2014 clonazolam re-emerged in illicit drug markets, with notification to the European Union Early Warning System in 2015 following the detection in a Swedish drug seizure [2]. Clonazolam continues to be detected within global illicit drug seizures, with a parallel increase in clonazolam-related enquires to poisons information centres [3,4]. Currently, there is only one non-fatal clonazolam mono-intoxication with analytical confirmation described in the literature [5]. More recently, a fatality attributed to clonazolam has also been described but does not detail the clinical toxidrome proximate to death [6].
Designer benzodiazepines: an update
Published in Expert Review of Clinical Pharmacology, 2023
Xiao Yu, H Karl Greenblatt, David J Greenblatt
The elimination half-lives for DBs are variable from drug to drug, and are a criterion for DB classification in much the same way as with prescribed benzodiazepines [25]. Half-life can influence the duration of action after single doses, as well as the rate and extent of drug accumulation associated with chronic treatment and discontinuation. The short half-life DBs include clonazolam and etizolam, with values in the range of 3–7 h. Drugs like diclazepam, meclonazepam, norflurazepam, and flubromazepam are long half-life compounds, with a half-life range of 40 h-110 h (Table 1). After overdosage or intoxication with DBs, the elimination half-life is likely to influence the time-course of recovery.