Designer Benzodiazepines: Effects, Toxicity, and Interactions

Abstract

Purpose: Although designer benzodiazepines (DBZDs) constitute a minor part of new psychoactive substances, they deserve the greatest attention because of their popularity among drug users and increasing number and availability. This review covers the effects of different DBZDs, available pharmacological evaluation tools, and their reported toxicity and potential pharmacodynamic and pharmacokinetic interactions with other drugs commonly co-abused with DBZDs.Methods: For this narrative review, a nonsystematic search was performed on PubMed, EMBASE, Google Scholar, and PubMed Central databases between June and July 2021. Results:The current consensus hypothesis suggests that DBZDs mediate their effects through interactions with the GABA A receptor, producing similar effects to benzodiazepines used in therapy, including sedation, hypnosis, anxiolysis, muscle relaxation, euphoria, amnesia, and addiction. Owing to the complexity of their action mechanism and the numerous GABA A subtype receptors, the pharmacodynamic metrics of DBZDs are very difficult to establish. The pharmacological effects of DBZD are related to their structure, influencing their binding to GABA A receptor subunits. Quantitative structure-activity relationship studies successfully predicted the biological activity and relative potency of DBZD but could not predict the main pharmacological effect of a given DBZD. Exploring the effects by netnographic studies is one of the available alternatives, despite its limitations. DBZDs are usually identified in the context of polysubstance use. Pharmacodynamic interactions between DBZDS and other CNS depressants, such as opioids, have been extensively reported. However, pharmacokinetic interactions between DBZDs and opioids are considered less important, and contradictory conclusions about their clinical significance have been reported. Conclusions:Understanding the mechanism of action and other pharmacological metrics is highly important in the clinical management of DBZDs.

2023 Guidelines on the Diagnosis and Treatment of Insomnia in Adults – Brazilian Sleep Association

“…152 Although there has been a decline in prescription in the past 20 years, 153 BZDs remain popular [153][154][155] with new formulations emerging as recreational drugs, the so-called designer BZDs. 156 Mechanism of action: They act as allosteric agonists of GABA-A type A receptorsi.e., they bind to the same receptor, but in different GABA sites, facilitating the effect of the agonist neurotransmitter. This effect is predominantly in postsynaptic neurons, where there is a cellular influx of chloride leading to neuronal hyperpolarization.…”