Isotonitazene: Fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland

Mueller, F.; Bogdal, Christian; Pfeiffer, Bernhard; Andrello, L.; Ceschi, Alessandro; Thomas, Aurélien; Grata, Elia

doi:10.1016/j.forsciint.2021.110686

Cited by 44 publications

(35 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together with other predicted properties, that is high GIA, and the possibility to cross BBB, ETZ is a potential neurotoxicant. This assumption is supported by the fact that analysis of post-mortem samples revealed a high accumulation of isotonitazene in the brain and pericardial fluids 30 . This compound is another benzimidazole-derived opioid analgesic drug related to ETZ, and was characterized as stronger than ETZ (MOR-βarr2, EC 50 = 1.63 nM; MOR-mini-Gi, EC 50 = 3.72 nM).…”

Section: Resultsmentioning

confidence: 90%

Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative

Kurach

Chłopaś-Konowałek²,

Budzyńska

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Synthetic opioids are gaining more and more popularity among recreational users as well as regular abusers. One of such novel psychoactive substance, is etazene, which is the most popular opioid drug in the darknet market nowadays. Due to limited information available concerning its activity, we aimed to characterize its developmental toxicity, including cardiotoxicity with the use of in vivo Danio rerio and in silico tools. Moreover, we aimed, for the first time, to characterize the metabolite of etazene, which could become a potential marker of its use for future forensic analysis. The results of our study proved severe dose-dependent developmental toxicity of etazene (applied concentrations 10–300 µM), including an increase in mortality, developmental malformations, and serious cardiotoxic effects, as compared with well-known and used opioid—morphine (applied concentrations 1–50 mM). In silico findings indicate the high toxic potential of etazene which may lead to drug-drug interactions and accumulation of substances. Furthermore, phase I metabolite of etazene resulting from N-dealkylation reaction was identified, and therefore it should be considered as a target for toxicological screening. Nonetheless, the exact mechanism of observed effects in response to etazene should be further examined.

show abstract

Section: Resultsmentioning

confidence: 90%

Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative

Kurach

Chłopaś-Konowałek²,

Budzyńska

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Isotonitazene was the first of the nitazenes that recently (re-)appeared on the drug market, where it has since been involved in multiple fatalities. 7,22,[31][32][33][34] The exact role of isotonitazene in these deaths, however, often remains speculative. 22 Additionally, based on the results presented here, the presence of (one or more) active metabolite(s) may also contribute to the observed toxicity.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Chemical Characterization, and μ-Opioid Receptor Activity Assessment of the Emerging Group of “Nitazene” 2-Benzylbenzimidazole Synthetic Opioids

Vandeputte

Uytfanghe

Layle

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…N -Desethylisotonitazene (metabolite of isotonitazene) ~ 1000 0.614 Identified as a metabolite of isotonitazene in 2019, USA [ 52 ] na LC–QTOF-MS [ 51 ] GC–MS [ 51 ] 3. Isotonitazene 500 1.63 Found at Europe drug market in 2019 [ 53 ] At least several hundred fatalities in Europe and North America [ 61 ] (0.59–2.28 ng/mL [ 61 ]) LC–QTOF-MS [ 65 ] GC–MS [ 65 ] 4. Protonitazene 200 3.95 Identified in blood sample in 2021, USA [ 54 ] na GC–MS [ 53 ] LC–QTOF-MS [ 54 ] 5.…”

Section: Benzimidazole Opioidsmentioning

confidence: 99%

“…The fatalities involved in the benzimidazole opioids were reported mainly for in etonitazene [ 59 ], isotonitazene [ 60 , 61 ], and metonitazene [ 55 ]; top fatalities are found for isotonitazene (Table 4 ). On the “Human deaths” column of Table 4 , there are many compounds without fatality data available (“na”), implying that deaths involved in other compounds of benzimidazole opioids will appear in the near future.…”

Section: Benzimidazole Opioidsmentioning

confidence: 99%

Non-fentanyl-derived synthetic opioids emerging during recent years

2022

View full text Add to dashboard Cite

Purpose Since the appearance of fentanyl followed by its many kinds of analogues around 1988, North America has been exposed to fierce synthetic opioid pandemic resulting in more than 130,000 deaths due to their overdoses until May 2019, when China declared to prohibit the licit fentanyl analog production. However, the Chinese announcement did not go into force in USA due to the adroit strategies of tough traffickers. Thus, contrary to the expectation, the number of synthetic opioid products and their poisoning cases in USA has increased by about 30%; especially, various benzimidazole synthetic opioids have revived on the illicit drug market during a recent few years. In this article, the recent abrupt changes in the situations of illicit synthetic opioid market and their current abuses are described. Methods Various databases, such as SciFinder, Google, and Google Scholar, were utilized to collect relevant reports referring old but newly appearing synthetic opioids. Results At the present time, there are several families of new synthetic opioids, which are not fentanyl derivatives; MT-45 and its analogs, benzamide and 2-phenylacetamide opioids (U-series opioids), and benzimidazole opioids. Most of the above substances had been developed in 1950s to 1970s, but had never been used as analgesic medicines, because of their severe adverse effects, such as respiratory depression, physical dependence, and resulting deaths. However, there is possibility that these drugs will become main illicit synthetic opioids in place of the fentanyl analogs during coming several years from this time. Conclusions All of the above non-fentanyl-derived families had been developed 50–70 years ago to establish them as analgesic medicines, but had been unsuccessful. These drugs largely appeared in the illicit drug markets in North America, Europe, and Australia, during recent years. Pharmacological, toxicological, and metabolic studies are insufficient for benzamide and 2-phenylacetamide opioids, and are very scant especially for benzimidazole opioids. This time we should start studying pharmacotoxicology of the newly emerging synthetic opioids to alert forensic toxicologists in the world and to suppress their rapid and wide spread in the world. Supplementary Information The online version contains supplementary material available at 10.1007/s11419-022-00624-y.

show abstract

Isotonitazene: Fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland

Cited by 44 publications

References 23 publications

Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative

Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative

Synthesis, Chemical Characterization, and μ-Opioid Receptor Activity Assessment of the Emerging Group of “Nitazene” 2-Benzylbenzimidazole Synthetic Opioids

Non-fentanyl-derived synthetic opioids emerging during recent years

Contact Info

Product

Resources

About