Evaluation of rewarding effects of nitazene analogs: results from conditioned place preference tests and <i>in vivo</i> microdialysis experiments in mice

The Journal of Toxicological Sciences, Journal Year: 2025, Volume and Issue: 50(1), P. 33 - 43

Published: Jan. 1, 2025

In illicit drug markets, the most recently expanding new synthetic opioid subclass is benzimidazoles, also known as nitazenes, which were originally developed analgesics in 1950s. The emergence of this classical, potent family has attracted extensive research interest field forensic toxicology; however, information on their psychological and physical dependence very limited. Herein, we evaluated rewarding effects four nitazene analogs using a battery vivo experiments, with positive control (isotonitazene). test materials, metonitazene, etodesnitazene, metodesnitazene, flunitazene, administered to male C57BL/6J mice by i.p. administration at 0.5, 2, 20, 20 mg/kg, respectively. comprehensive behavioral observation tests, representative opioid-related physiological states, including analgesia, stereotypic circling behavior, hyperlocomotion, Straub tail response, observed. A set conditioned place preference tests revealed that all induced palatability mice. Furthermore, measurements dopamine levels nucleus accumbens shell microdialysis resulted significant elevations material-treated groups, suggesting nitazenes elicit effect through neural circuit originating from μ-opioid receptor activation ventral tegmental area. Our findings add important data regarding highlight abuse potential these materials other prevailing analogs.

Language: Английский

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Analysis of NPS in post-mortem samples in forensic toxicology

Comprehensive analytical chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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The UHPLC-MS/MS method for the determination of 26 synthetic benzimidazole opioids (nitazene analogs) with isomers separation

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2025, Volume and Issue: 260, P. 116796 - 116796

Published: March 5, 2025

Language: Английский

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Early identification of the use of potent benzylbenzimidazoles (nitazenes) through wastewater analysis: Two years of data from 22 countries

Addiction, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Background and Aims The use of new synthetic opioids, such as the highly potent 2‐benzylbenzimidazoles (i.e. nitazene) drugs, is a global health concern because their increased risk fatal overdose. In early 2020s, nitazene analogues were linked to significant numbers overdoses in United States. Their reach now worldwide, with overdose deaths reported Europe, Australia New Zealand. aim this study was measure quantities nitazenes wastewater samples collected from 68 locations 22 countries, covering six continents, understand estimate use. Methods Untreated influent over one‐week period that included Year 2022–2023 2023–2024. Samples countries: Australia, Austria, Belgium, Brazil, Canada, Chile, China, Cyprus, Czechia, France, Germany, Greece, Iceland, Italy, Zealand, Nigeria, Republic Korea, Slovenia, Spain, Sweden, Kingdom loaded onto solid‐phase extraction cartridges country collection sent for elution analysis using sensitive liquid chromatography–mass spectrometry methods. Results A total 683 individual analysed across two years: 339 344 Two analogues—protonitazene N‐pyrrolidino etonitazene (etonitazepyne)—were found five separate sites States Australia. period, protonitazene following year, detected further States, while both etonitazepyne one site Protonitazene mass loads ranged between 0.3 mg/day/1000 people 100 people. Etonitazepyne also at 0.2–2 people). Conclusions very high load calculated, analysis, day 30 December 2023 showed same trend lower base. Wastewater‐based surveillance shows promise form drug warning ongoing monitoring trends use, especially complementary tool existing

Language: Английский

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Evaluation of enzyme‐linked immunosorbent assay screening kits for the detection of nitazene analogs

Journal of Forensic Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Nitazene analogs are a highly potent class of novel psychoactive substances (NPS) that were first identified in forensic casework the United States 2019. While enzyme‐linked immunosorbent assay (ELISA) remains prevalent screening tool toxicology laboratories, no nitazene‐specific ELISA kits commercially available, supporting use high‐resolution mass spectrometry (HRMS) methods as more adaptable alternative for screening. However, even with growth popularity HRMS techniques, it is important to understand cross‐reactivity substances, such nitazenes, routinely used kits. Cross‐reactivity particularly since can impact reliability results, potentially leading non‐detection or false‐positive identifications presence non‐target analytes. This study tested seven nitazene (4′‐OH nitazene, 5‐methyl etodesnitazene, isotonitazene, metodesnitazene, N‐piperidinyl etonitazene, N‐pyrrolidino and protonitazene) whole blood using 13 commercial from three manufacturers. Various drug/class selected based on reported potential co‐positivity nitazenes (opiates, opioids, fentanyl) by structural similarities (LSD, zolpidem). Across concentrations analytes, none produced signal sufficient positive result, confirming their at these levels does not compromise specificity target findings highlight need laboratories adopt spectral‐based like advocate development effective analog

Language: Английский

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Navigating nitazenes: A pharmacological and toxicological overview of new synthetic opioids with a 2-benzylbenzimidazole core

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110470 - 110470

Published: April 1, 2025

Language: Английский

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Nitazene test strips: a laboratory evaluation

Harm Reduction Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 28, 2024

2-Benzylbenzimidazole 'nitazene' opioids pose a growing threat to public health. Nitazene analogues are increasingly found mixed with or (mis)sold as heroin and in falsified (non-)opioid medications, posing great risk of intoxication users (un)knowingly exposed these potent opioids. Lateral flow immunoassay nitazene test strips (NTS; BTNX Rapid Response™) became commercially available Q1 2024, the aim enable rapid detection drug samples. As only limited independent data is on performance strips, this lab-based study aimed at evaluating their potential for checking applications.

Language: Английский

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Detection of N-desethyl etonitazene in a drug checking sample: chemical analysis and pharmacological characterization of a recent member of the 2-benzylbenzimidazole “nitazene” class

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2024, Volume and Issue: 251, P. 116453 - 116453

Published: Aug. 25, 2024

The emergence of 2-benzylbenzimidazole "nitazene" opioids is stirring up the recreational synthetic opioid market. Many nitazene analogues act as potent agonists at µ‑opioid receptor (MOR), demonstrated in various vitro and vivo studies. Severe intoxication overdose deaths associated with are increasingly being reported. Nitazene classified a public health threat, stressing need for close monitoring new developments on drug This study reports detection N-desethyl etonitazene sample handed by user Swiss checking service August 2023. person bought through an internet source where it was stated to contain isotonitazene. Chemical analyses were conducted characterize sample, i.e. nuclear magnetic resonance (NMR), capillary electrophoresis (CE), high-resolution mass spectrometry (HRMS). additionally investigated using two different MOR activation assays. NMR high-performance liquid chromatography (HPLC) coupled HRMS confirmed presence high purity absence isotonitazene etonitazene. N-Desethyl have been detected before metabolites However, first seen isotonitazene, they now emerging standalone drugs. applied bioassays increased efficacy approximately 6-9-fold higher potency compared fentanyl. showed EC

Language: Английский

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The State of the Art in Post-Mortem Redistribution and Stability of New Psychoactive Substances in Fatal Cases: A Review of the Literature

Psychoactives, Journal Year: 2024, Volume and Issue: 3(4), P. 525 - 610

Published: Dec. 4, 2024

In post-mortem (PM) investigations, forensic toxicologists attempt to identify legal or illegal substances present before death and determine how they contributed the cause of death. A critical challenge is ensuring that PM sample concentrations accurately reflect those at time death, as postmortem redistribution (PMR) can alter these levels due anatomical physiological changes. The PMR phenomenon called a ‘toxicological nightmare’. significantly affects drug concentrations, particularly for lipophilic drugs with high volume distribution. emergence new psychoactive (NPSs) has led growing recognition their role significant public health concern, frequently associated fatalities related polydrug use. These are renowned ability induce intoxication low doses, which continuous updating toxicological methods improve detection adopt analytical standards. comprehensive NPS metabolites, some still undiscovered, presents an additional challenge, do metabolic pathways. This complicates identification in fatal cases using standard methods, potentially leading underestimation actual prevalence results. Furthermore, interpretation results hindered by absence data on blood specific contributions causes exacerbated lack knowledge whether influences them. paper review literature involving various NPS, categorized according classifications United Nations Office Drugs Crime (UNODC) European Union Agency (EUDA). categories include cathinones, phenylethylamines, arylalkylamines, phencyclidine-type substances, phenmetrazines, piperazines, phenidates, aminoindanes, LSD-like NPSs, tryptamines, fentanyl analogs, designer benzodiazepines, synthetic cannabinoids, nitazenes. covers not only but also stability studied, analysis, attempts shed light phenomenon. used key terms, such PMR, names previously analyses across multiple peer-reviewed journals databases, including Scopus, Google Schoolar, Springer, PubMed, Wiley Online Library. addition, references from retrieved articles were examined relevant research. Interpreting complex lacks definitive guidelines, requiring nuanced understanding its challenges potential pitfalls. As result, toxicology often regarded art. primary aim this provide framework assist evaluation analysis. guide intended complement existing practices applied laboratories within analysis cases.

Language: Английский

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Characterization of novel nitazene recreational drugs: Insights into their risk potential from in vitro µ-opioid receptor assays and in vivo behavioral studies in mice

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107503 - 107503

Published: Nov. 7, 2024

2-Benzylbenzimidazole derivatives or 'nitazenes' are increasingly present on the recreational drug market. Here, we report synthesis and pharmacological characterization of 15 structurally diverse nitazenes that might be predicted to emerge grow in popularity. This work expands existing knowledge about 2-benzylbenzimidazole structure-activity relationships (SARs), while also helping stakeholders (e.g., forensic toxicologists, clinicians, policymakers) their risk assessment preparedness for potential next generation nitazenes. In vitro µ-opioid receptor (MOR) affinity was determined via competition radioligand (

Language: Английский

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