Blake Curtis

Designer benzodiazepines (DBZDs) are a class of new psychoactive substances (NPS) designed as legal alternatives to prescription BZDs. Bromazolam has been the most prevalent DBZD detected on the recreational market around the world; however, a new DBZD, ethylbromazolam (8-bromo-1-ethyl-6-phenyl-4 H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine; also known as bromoethylazolam) has recently emerged. In this study, the emergence of ethylbromazolam in Canada, the UK, and Australia is reported based on analysis of samples from drug checking services and in Germany based on analysis of samples seized by customs and mail services. Since November 2024, ethylbromazolam has been increasingly detected with a concurrent decrease in bromazolam detections, suggesting that its emergence is likely in response to the international control of bromazolam on 3rd December 2024. Additionally, increased detections of other DBZDs, including desalkylgidazepam (bromonordiazepam) and clobromazolam (phenazolam) have been recently observed. The in vitro α ₁ β ₂ γ ₂ GABA _A receptor activity of ethylbromazolam was determined using an automated patch clamp assay. Ethylbromazolam was found to have similar in vitro GABA _A receptor activity as bromazolam (EC ₅₀ of 10.1 nM and 15.2 nM, respectively), indicating comparable pharmacological activity and potential for harm. The market should continue to be monitored closely as it continues to evolve in response to the control of bromazolam.

2-Benzylbenzimidazole opioids and related derivatives, also known as ‘nitazenes’, present a growing threat to public health. Emerging in Europe in 2019, the nitazene group of drugs is a recent addition to the novel synthetic opioid class and has been associated internationally with adverse effects in drug users, overdose clusters and significant mortality. The high potency of many nitazene derivatives, which can in many cases exceed that of fentanyl, poses a significant challenge to the public health and early warning systems used to detect and respond to the emergence of new high-risk substances. This report describes close collaboration between an Australian drug checking service and a nearby university laboratory to identify and characterise the novel synthetic opioid N-pyrrolidino isotonitazene in an expected oxycodone sample presented by a member of the public. Though no prior publications are available describing the presence of this nitazene in the drug market, previously reported in vitro evaluation of this compound reveals it to be among the most potent nitazene opioid agonists known. The study highlights the rapid response possible though engaging drug users with drug checking services as a market monitor and early warning system to alert health services and the broader community to the presence of unexpected, high-risk substances. Integration of well-resourced and supported drug checking services provides a powerful approach to tackle the public health threats associated with new synthetic opioids and other drugs of concern.

Parasites, such as the malaria parasite P. falciparum , are critically dependent on host nutrients. Interference with nutrient uptake can lead to parasite death and, therefore, serve as a successful treatment strategy. P. falciparum parasites cannot synthesise cholesterol, and instead source this lipid from the host. Here, we tested whether cholesterol uptake pathways could be ‘hijacked’ for optimal drug delivery to the intracellular parasite. We found that fluorescent cholesterol analogues were delivered from the extracellular environment to the intracellular parasite. We investigated the uptake and inhibitory effects of conjugate compounds, where proven antimalarial drugs (primaquine and artesunate) were attached to steroids that mimic the structure of cholesterol. These conjugated antimalarial drugs improved the inhibitory effects against multiple parasite lifecycle stages, multiple parasite species, and drug-resistant parasites, whilst also lowering the toxicity to human host cells. Steroids with introduced peroxides also displayed antimalarial activity. These results provide a proof-of-concept that cholesterol mimics can be developed as a drug delivery system against apicomplexan parasites with the potential to improve drug efficacy, increase therapeutic index, and defeat drug resistance.