Intoxications in an Australian Emergency Department Involving ‘Nitazene’ Benzylbenzimidazole Synthetic Opioids (Etodesnitazene, Butonitazene and Protonitazene)

Abstract

Benzimidazole synthetic opioids are highly potent μ-opioid receptor agonists with heroin-like effects, including dose-dependent respiratory depression and a high risk of abuse and toxicity. Benzimidazoles were first detected in 2019 in Europe and Canada, with analytical confirmation of etodesnitazene, protonitazene and butonitazene in 2021. We report the first detections of these compounds in Australia, in two patients presenting with drug toxicity to Emergency Departments in the state of Victoria. Case 1 was a female in her 20s who rectally administered etodesnitazene and was found unconscious with a respiratory depression and hypotension. Case 2 was a female in her 30s who presented to the ED in a sedated state after taking a formulation of protonitazene which also contained butonitazene, in addition to methylamphetamine. She responded positively to naloxone. Novel synthetic opioids were used with prior experience of the formulations purchased, however the unpredictability of their effects was demonstrated by the acute toxicity experienced with this occasion of use. Toxicosurveillance of Emergency Department presentations with analytical confirmation of drugs is crucial in identifying emerging drugs in the community and informing harm reduction strategies.

Adulteration and substitution of drugs purchased in Australia from cryptomarkets: An analysis of Test4Pay

“…Furthermore, while adulterated MDMA was uncovered through CanTEST resulting in a community notice [14] and has featured in recent Victorian alerts [35], the MDMA tested via Test4Pay was entirely MDMA. The appearance of nitazenes in the Australian drug supply, albeit sold as labelled, is concerning, and fits with a recent alert distributed in Victoria of metonitazene being sold as cocaine [36] and case reports of Victorian emergency department presentations following the use of nitazenes [37].…”

An intoxication involving 2‐methyl AP‐237 and AP‐238 from Victoria, Australia: Case report

“…This case is the first in Australia to analytically confirm the use of 2‐methyl AP‐237 and AP‐238 in a clinical case. Growing reports of NSOs throughout the world and Australia's close proximity to China and India where the majority of these compounds is manufactured suggests that more NSOs are likely to infiltrate the Australian market 8,24,25 . The role of early detection and warning to consumers, health administrators, and clinicians is crucial in managing the impacts of these often highly potent NPS.…”

Analysis of highly potent synthetic opioid nitazene analogs and their positional isomers

“…4 Recently, several benzimidazole opioids, such as metonitazene and isotonitazene, have appeared on the drug market and have caused many intoxication cases. [5][6][7][8][9] A Swiss chemical company (CIBA Aktiengesellschaft) developed benzimidazole synthetic opioids in the late 1950s. 10 Among the many compounds synthesized, etonitazene (Table 1) showed the strongest antinociceptive activity in mice; it was 1,000 times more potent than morphine.…”

“…Among the newcomers, benzimidazole derivatives have been drawing much attention owing to their strong activity, often exceeding that of fentanyl 4 . Recently, several benzimidazole opioids, such as metonitazene and isotonitazene, have appeared on the drug market and have caused many intoxication cases 5–9 . A Swiss chemical company (CIBA Aktiengesellschaft) developed benzimidazole synthetic opioids in the late 1950s 10 .…”