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Mortality Associated with Nitazenes May Be Underestimated Due to Post-Mortem Degradation 与nitazene相关的死亡率可能因死后降解而被低估
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100207
S. Chen, R. Moore, S. Hudson, C. Copeland

Introduction

Nitazenes are highly potent synthetic opioids that are being increasingly detected in the UK illicit drug market. Following reports from toxicologists of inconsistent post-mortem test results, we investigated the stability of nitazenes in post-mortem tissues and performed pharmacoepidemiological modelling to understand the impact nitazene degradation may be having on mortality statistics.

Methods

In vivo study: rats (n=12) were administered a nitazene with post-mortem samples taken on post-mortem Day 1 and Day 7 to assess pre-sampling stability. These samples were then stored in the fridge for 1 month and re-tested to assess post-sampling stability. Pharmacoepidemiology study: Nitazene cases were extracted from the National Programme on Substance Use Mortality with exponential smoothing modelling performed to assess forecasted and actual trends in non-nitazene deaths.

Results

All three nitazenes tested (metonitazene, n-desethyl isotonitazene, n-pyrrolidino etonitazene) degraded in post-mortem blood. On average only 14% of the nitazene detected in the Day 1 samples which were tested immediately remained in the Day 7 samples stored in the fridge for 1 month (n=12). Pharmacoepidemiological modelling revealed a 30% increase in excess death in areas with known nitazene outbreaks in 2023.

Conclusions

Nitazene-related-deaths are likely being underestimated due to their degradation in post-mortem blood samples.
nitazene是一种强效的合成阿片类药物,在英国非法药物市场上被越来越多地发现。根据毒理学家关于不一致的死后检测结果的报告,我们调查了nitazene在死后组织中的稳定性,并进行了药物流行病学建模,以了解nitazene降解可能对死亡率统计数据的影响。方法活体研究:大鼠(n=12)在死后第1天和第7天采集尸体样本,同时给予nitazene,以评估取样前的稳定性。然后将这些样品在冰箱中保存1个月,并重新测试以评估取样后的稳定性。药物流行病学研究:从国家物质使用死亡率方案中提取尼Nitazene病例,采用指数平滑模型评估非尼Nitazene死亡的预测和实际趋势。结果三种nitnitazene (metoitazene、n-去乙基异硝基苯、n-吡咯烷基异硝基苯)在死后血液中均有降解。在第1天的样品中检测到的nitazene中,平均只有14%立即在第7天的样品中保存在冰箱中1个月(n=12)。药物流行病学模型显示,2023年已知硝基苯爆发地区的超额死亡人数增加了30%。结论尼他嗪相关死亡人数可能被低估,因为其在死后血液样本中降解。
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引用次数: 0
Monitoring the Results of Chemical-Toxicological Studies of New Psychoactive Substances in the Sverdlovsk Regional Center for the Treatment of Acute Poisoning in 2015–2025 2015-2025年斯维尔德洛夫斯克地区急性中毒治疗中心新型精神活性物质化学毒理学研究结果监测
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100225
M. Gofenberg

Introduction

According to the Sverdlovsk Regional Center for the Treatment of Acute Poisoning, more than 30% of all acute chemical poisonings are associated with the use of narcotic drugs and novel psychoactive substances (NPS).

Methods

Retrospective study of laboratory data on all cases of acute poisoning with narcotic, psychotropic and new psychoactive substances in the Sverdlovsk Regional Poisoning Treatment Center, Yekaterinburg, Russia, from January 2015 to January 2025. Screening chemical-toxicological examination of urine of patients with acute poisoning was performed using the gas chromatography mass spectrometry (GC-MS) method.

Results

For 10 years, the main group of substances detected in acute poisonings in the Sverdlovsk region have been substances with psychostimulant action. In 2015–2025, in the Sverdlovsk region, both structural analogues of methamphetamine have become widespread and pyrrolidino-substituted cathinones. Since 2023, a significant number of acute poisonings with 4-chloromethylcathinone have been detected. The number of acute poisonings with synthetic cannabimimetics has decreased, but the number of acute poisonings with opioids (methadone) has increased, including fatal ones. Since 2023, the number of poisonings from Amanita mushrooms and dietary supplements containing dried pieces of these mushrooms has increased. At the same time, cases of polydrug addiction are increasingly being identified, when the use of more than one drug is recorded combined use of new psychoactive substances, medications (neuroleptics, baclofen, etc.), veterinary drugs, 1,4-butanediol, gamma-hydroxybutyric acid and alcohol.

Conclusions

The detection rate of various compounds in chemical-toxicological studies changes over time, but the main group of NPS detected in laboratory diagnostics of acute poisoning over 10 years are synthetic cathinones. The most severe cases of acute poisoning, including fatal ones, are associated with the combined use of drugs, medications and NPS.
根据斯维尔德洛夫斯克地区急性中毒治疗中心的数据,超过30%的急性化学中毒与使用麻醉药品和新型精神活性物质(NPS)有关。方法回顾性分析2015年1月至2025年1月俄罗斯叶卡捷琳堡斯维尔德洛夫斯克地区中毒治疗中心所有急性麻醉药品、精神药物和新型精神活性物质中毒病例的实验室资料。采用气相色谱-质谱(GC-MS)法对急性中毒患者尿液进行筛选化学毒理学检查。结果10年来,斯维尔德洛夫斯克地区急性中毒事件中检测到的主要物质为具有精神兴奋作用的物质。2015-2025年,在斯维尔德洛夫斯克地区,甲基苯丙胺的结构类似物和吡咯烷二取代的卡西酮都变得普遍。自2023年以来,已发现大量4-氯甲基卡西酮急性中毒病例。合成大麻模拟物的急性中毒数量有所减少,但阿片类药物(美沙酮)的急性中毒数量有所增加,包括致命的。自2023年以来,因毒伞菌和含有干毒伞菌的膳食补充剂而中毒的人数有所增加。与此同时,越来越多的多药成瘾病例被发现,记录使用一种以上的药物,同时使用新的精神活性物质、药物(神经抑制剂、巴氯芬等)、兽药、1,4-丁二醇、γ -羟基丁酸和酒精。结论化学毒理学研究中各种化合物的检出率随时间而变化,但10年以上急性中毒实验室诊断中检出的NPS主要为合成卡西酮类。最严重的急性中毒病例,包括致命的病例,与药物、药物和NPS的联合使用有关。
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引用次数: 0
Mapping the Emergence of New Psychoactive Substances in Brazil (2019–2025): A national survey supporting the Brazilian Early Warning System 绘制巴西新精神活性物质的出现(2019-2025):一项支持巴西预警系统的全国性调查
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100222
G. Giudice

Introduction

In recent years, Brazil has seen an increase in the circulation of NPS. While forensic laboratories have reported isolated detections, no comprehensive national survey has been conducted. To address this gap, the Center for Studies on Drugs and Community Social Development (CDESC) launched an online survey targeting focal points from forensic institutions in all Brazilian states. CDESC is a project involving UNODC, the National Secretariat for Drug Policy and Asset Management (SENAD/MJSP), and UNDP.

Methods

A chemist made the survey design and the form. The data team implemented the form using Google Apps Script with JavaScript, a free and accessible tool for nationwide data collection.

Results

At the time of submission, data collection is ongoing. So far, 23 laboratories have responded, representing all five Brazilian regions. Only two reported no NPS detections during the period. The others identified a range of substances, highlighting documentation gaps and operational challenges.

Conclusions

This retrospective mapping provides unprecedented insights into NPS presence and diversity, reinforcing the need for coordinated monitoring efforts. The findings directly informed the priorities of the newly established Early Warning System.
近年来,巴西NPS的流通有所增加。虽然法医实验室报告了孤立的发现,但没有进行全面的全国调查。为了解决这一差距,毒品和社区社会发展研究中心(CDESC)发起了一项针对巴西各州法医机构联络点的在线调查。该项目涉及毒品和犯罪问题办公室、国家毒品政策和资产管理秘书处(SENAD/MJSP)和开发计划署。方法由化学家进行调查设计和问卷调查。数据团队使用谷歌Apps Script和JavaScript实现了这个表单,这是一个免费的、可访问的全国性数据收集工具。结果在提交时,数据收集正在进行中。到目前为止,23个实验室做出了回应,代表了巴西所有五个地区。在此期间,只有两家报告没有检测到NPS。其他人则确定了一系列实质内容,强调了文件差距和业务挑战。结论回顾性制图为NPS的存在和多样性提供了前所未有的见解,加强了协调监测工作的必要性。调查结果直接说明了新建立的早期预警系统的优先事项。
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引用次数: 0
Police Seizure of Drugs and Other Psychoactive Substances in a Northern Region of Russia 警方在俄罗斯北部地区查获毒品和其他精神活性物质
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100221
A. Gil

Introduction

Drugs and psychoactive substances is a continuous problem in Russia and worldwide. Northern industrial regions of Russia, including Khanty-Mansi Autonomous Okrug-Yugra (KhMAO-Yugra), are vulnerable to the epidemic of drug use due to: the higher level of economic development, intensive migration, severe northern climate.

Methods

The data on police seizure of drugs for 2024 in KhMAO-Yugra was analyzed. Results and

Conclusions

The region's black market is dominated by stimulants and other synthetic drugs (197kg or 88.2% of all seized drugs) with their illegal trafficking continuing to pose the main threat. Stimulants were mainly represented by amphetamine-type drugs (1272 cases of seizure): N-methylephedrine analogues (α-PVP), mephedrone, and MDMA. Non-synthetic drugs of the cannabis and opium groups accounted for only 9.1% and 0.3% of the seized drugs, respectively. Compared to 2003, the amount of methadone seized increased by 7% (from 1.4kg to 1.5kg), heroin – decreased by 99.3% (from 57.3kg to 0.4kg), cocaine – increased 22-fold (from 3g to 66g). Drugs are usually distributed contactlessly and enter the region predominantly by motor transport from other regions of the country mainly situated in the Urals Federal District. Criminal groups, commonly originating countries of Central Asia, retain a significant control over illegal drugs distribution.
毒品和精神活性物质在俄罗斯和全世界都是一个持续存在的问题。俄罗斯北部工业区,包括汉特-曼西自治区奥克鲁格-尤格拉(khmaoyugra),由于经济发展水平较高,移民密集,北方气候恶劣,易受吸毒流行的影响。方法对高毛-尤格拉地区警方查获毒品的数据进行分析。结果与结论该地区黑市以兴奋剂和其他合成毒品为主(197公斤,占缴获毒品总量的88.2%),非法贩运继续构成主要威胁。兴奋剂主要以安非他明类药物(1272例)为代表:n -甲基麻黄碱类似物(α-PVP)、甲氧麻黄酮和MDMA。大麻及鸦片类非合成毒品分别只占检获毒品的9.1%及0.3%。与二零零三年比较,检获的美沙酮增加7%(由1.4公斤增至1.5公斤),海洛英减少99.3%(由57.3公斤减至0.4公斤),可卡因则增加22倍(由3克增至66克)。药物通常以非接触方式分发,主要通过汽车运输从主要位于乌拉尔联邦区的该国其他地区进入该地区。犯罪集团通常是中亚的原产国,它们对非法毒品的分销保持着很大的控制。
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引用次数: 0
Field Quantification of MDMA in Seized Samples Using Portable NIR Spectroscopy 便携式近红外光谱法现场定量检获样品中的MDMA
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100231
B. Jurásek, E. Vedralová, M. Martinec, M. Kuchař

Introduction

MDMA represents one of the most commonly used illicit stimulant in Europe. Traditional analytical methods for MDMA analysis are time-consuming and require laboratory facilities, limiting field applications. Near-infrared (NIR) spectroscopy offers rapid, non-destructive identification and quantification capabilities suitable for on-site forensic analysis.

Methods

Instrumentation: A MicroNIR On-Site-W spectrometer with 3D-printed sample holder. Calibration sets: Binary mixtures of MDMA hydrochloride (10–90% w/w) were prepared with cutting agents: caffeine, talc, magnesium stearate, and microcrystalline cellulose. Data analysis: Spectral preprocessing included detrending, Savitzky-Golay first and second derivative, and standard normal variate (SNV) normalisation. Principal component analysis (PCA) and principal component regression (PCR) models were developed using CAMO Unscrambler X with 5 principal components. Validation: Street samples (n=39) seized by law enforcement agencies in the Czech Republic.

Results

The measured NIR spectra from the calibration sets were used to create PCA and PCR models. The street samples were measured by the NIR spectrometer and evaluated using the created models. The PCA models successfully differentiated MDMA from adulterants and the PCR models enabled us the quantification of the street MDMA samples. The purity of the street samples were confirmed by either GC-FID or HPLS-DAD.

Conclusions

Portable NIR spectroscopy paired with chemometric modeling provides a robust field-deployable solution for MDMA quantification. The approach supports rapid on-scene decision-making in drug enforcement operations.
mdma是欧洲最常用的非法兴奋剂之一。传统的MDMA分析方法耗时且需要实验室设施,限制了现场应用。近红外(NIR)光谱提供快速,非破坏性的识别和定量能力,适合现场法医分析。方法:微红外原位w谱仪,3d打印样品架。校正组:配制盐酸MDMA二元混合物(10-90% w/w),切割剂:咖啡因、滑石粉、硬脂酸镁和微晶纤维素。数据分析:光谱预处理包括去趋势、Savitzky-Golay一阶导数和二阶导数以及标准正态变量(SNV)归一化。采用CAMO Unscrambler X建立主成分分析(PCA)和主成分回归(PCR)模型,共5个主成分。验证:捷克共和国执法机构查获的街头样本(n=39)。结果利用标定集的近红外光谱建立了PCA和PCR模型。通过近红外光谱仪测量街道样本,并使用所创建的模型进行评估。PCA模型成功地将MDMA与掺假品区分开来,PCR模型使我们能够对街头MDMA样本进行量化。采用气相色谱- fid或高效液相色谱- dad对街道样品进行纯度鉴定。结论可移动的近红外光谱与化学计量建模相结合,为MDMA定量提供了一种可靠的现场可部署解决方案。该方法支持毒品执法行动的快速现场决策。
{"title":"Field Quantification of MDMA in Seized Samples Using Portable NIR Spectroscopy","authors":"B. Jurásek,&nbsp;E. Vedralová,&nbsp;M. Martinec,&nbsp;M. Kuchař","doi":"10.1016/j.etdah.2025.100231","DOIUrl":"10.1016/j.etdah.2025.100231","url":null,"abstract":"<div><h3>Introduction</h3><div>MDMA represents one of the most commonly used illicit stimulant in Europe. Traditional analytical methods for MDMA analysis are time-consuming and require laboratory facilities, limiting field applications. Near-infrared (NIR) spectroscopy offers rapid, non-destructive identification and quantification capabilities suitable for on-site forensic analysis.</div></div><div><h3>Methods</h3><div>Instrumentation: A MicroNIR On-Site-W spectrometer with 3D-printed sample holder. Calibration sets: Binary mixtures of MDMA hydrochloride (10–90% w/w) were prepared with cutting agents: caffeine, talc, magnesium stearate, and microcrystalline cellulose. Data analysis: Spectral preprocessing included detrending, Savitzky-Golay first and second derivative, and standard normal variate (SNV) normalisation. Principal component analysis (PCA) and principal component regression (PCR) models were developed using CAMO Unscrambler X with 5 principal components. Validation: Street samples (n=39) seized by law enforcement agencies in the Czech Republic.</div></div><div><h3>Results</h3><div>The measured NIR spectra from the calibration sets were used to create PCA and PCR models. The street samples were measured by the NIR spectrometer and evaluated using the created models. The PCA models successfully differentiated MDMA from adulterants and the PCR models enabled us the quantification of the street MDMA samples. The purity of the street samples were confirmed by either GC-FID or HPLS-DAD.</div></div><div><h3>Conclusions</h3><div>Portable NIR spectroscopy paired with chemometric modeling provides a robust field-deployable solution for MDMA quantification. The approach supports rapid on-scene decision-making in drug enforcement operations.</div></div>","PeriodicalId":72899,"journal":{"name":"Emerging trends in drugs, addictions, and health","volume":"5 ","pages":"Article 100231"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of Etodesnitazene Metabolites Using UHPLC-HRMS/MS in Various In Vitro and In Vivo Models 用UHPLC-HRMS/MS在体内体外模型中鉴定依托地尼氮代谢物
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100244
M. Mrňavá, P. Palivec, Š. Friedrichová, M. Kuchař

Introduction

Etodesnitazene, a synthetic benzimidazole opioid, has recently emerged drug market as a potent new psychoactive substance with significant abuse potential. Due to limited data on its metabolism, there is a critical need to elucidate its biotransformation pathways along with confirmation of the structures using synthesized standards for forensic and toxicological purposes.

Methods

In vitro incubations were performed using pooled human and rat liver microsomes, hepatocytes, and cytosolic fractions to assess both phase I and phase II metabolism. For in vivo studies, urine samples were collected from male Wistar rats. Analysis of all samples was performed by UHPLC-HRMS/MS, and metabolic pathways were determined using Compound Discoverer, FreeStyle and MassFrontier softwares. The selected metabolites were further synthesized and analyzed under the same conditions to confirm the structure.

Results

Across all models, several phase I and phase II metabolites were detected, including hydroxylated, N-dealkylated, and glucuronidated derivatives observed mainly in hepatocyte incubations and rat urine.

Conclusions

The combined use of in vitro and in vivo models provided a comprehensive overview of etodesnitazene metabolism. The data obtained (structure, m/z, RT, fragmentation spectra) can be utilized by forensic toxicology laboratories to confirm the presence of this substance in, for instance, urine, blood or hair samples of users. Concurrently, the confirmation and synthesis of our metabolite standards establish the foundation for future pharmacokinetic and pharmacodynamic studies.
乙托地尼氮是一种合成的苯并咪唑类阿片,近年来作为一种强效的新型精神活性物质出现在药物市场上,具有严重的滥用潜力。由于其代谢数据有限,迫切需要阐明其生物转化途径,并使用法医和毒理学目的的合成标准确认其结构。方法采用人、大鼠肝微粒体、肝细胞和细胞质组分进行体外培养,评估I期和II期代谢。在体内研究中,收集了雄性Wistar大鼠的尿液样本。所有样品均采用UHPLC-HRMS/MS进行分析,并使用Compound Discoverer、FreeStyle和MassFrontier软件确定代谢途径。选择的代谢物在相同条件下进一步合成和分析以确定其结构。在所有模型中,检测到几种I期和II期代谢物,包括羟基化,n -脱烷基和葡萄糖醛酸衍生物,主要在肝细胞培养和大鼠尿液中观察到。结论体外和体内模型的联合应用提供了对依托地尼氮代谢的全面概述。获得的数据(结构、m/z、RT、碎片谱)可被法医毒理学实验室用来确认这种物质的存在,例如在使用者的尿液、血液或头发样本中。同时,我们的代谢物标准的确认和合成为未来的药代动力学和药效学研究奠定了基础。
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引用次数: 0
Synthesis and Characterization of Potentially Dangerous New Nitazene Analogues 潜在危险的新型Nitazene类似物的合成与表征
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100216
D.F.R. Ferreira, N.R. Neng, A.L.M.B.C. Quintas, H.M.G.G. Gaspar

Introduction

New Psychoactive Substances (NPS) are substances of abuse not controlled under the 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances, as defined by the United Nations Office on Drugs and Crime. Globally, over 1,350 NPS have been reported, including highly potent synthetic opioids. According to the European Union Drugs Agency, since 2009, 88 synthetic opioids have been detected on the European drug market. In 2024, seven new substances were reported, all belonging to the Nitazene class — highly potent compounds linked to overdose deaths. To date, 22 Nitazenes have been identified across Europe.

Methods

This research focuses on the synthesis of Nitazene derivatives based on the 2-benzylbenzimidazole scaffold. Structural diversity was achieved through substitutions at two key positions: (i) the ether moiety of the benzyl group and (ii) the benzimidazole core.

Results

The synthesised compounds were structurally characterised using Nuclear Magnetic Resonance spectroscopy and High-Resolution Mass Spectrometry to confirm their molecular structure and purity.

Conclusions

This study introduces new analogues to the Nitazenes, enriching the structural diversity of this emerging class of opioid. The characterised compounds can serve as analytical reference standards to support identification and monitoring of these substances in forensic and toxicological settings.
根据联合国毒品和犯罪问题办公室的定义,新的精神活性物质(NPS)是不受1961年《麻醉品单一公约》或1971年《精神药物公约》管制的滥用物质。在全球范围内,已报告了1350多种NPS,包括强效合成阿片类药物。据欧盟药品管理局称,自2009年以来,在欧洲药品市场上发现了88种合成阿片类药物。2024年,报告了七种新物质,都属于Nitazene类——与过量死亡有关的强效化合物。到目前为止,在欧洲已经发现了22种nitazene。方法以2-苄基苯并咪唑为骨架,合成硝基衍生物。结构多样性是通过两个关键位置的取代来实现的:(i)苯基的醚部分和(ii)苯并咪唑核心。结果利用核磁共振波谱和高分辨率质谱对合成的化合物进行了结构表征,确定了化合物的分子结构和纯度。结论本研究引入了nitazene的新类似物,丰富了这类新兴阿片类药物的结构多样性。所鉴定的化合物可作为分析参考标准,支持在法医和毒理学环境中对这些物质进行鉴定和监测。
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引用次数: 0
Exploring the Anticancer Potential of the Psychoactive Drug Sertraline: A Step Toward Repurposed Oncology Therapeutics 探索精神活性药物舍曲林的抗癌潜力:朝着重新定位肿瘤治疗迈出的一步
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100214
S. Fereydouni

Introduction

The search for novel anticancer therapies has led to the repurposing of psychoactive drugs. Sertraline, a selective serotonin reuptake inhibitor (SSRI), is emerging as a candidate for cancer treatment beyond its psychiatric use. Objectives: To evaluate the anticancer potential of sertraline on pancreatic cancer cells (PANC 1) and assess its dose-dependent cytotoxic effects.

Methods

PANC 1 cells were treated with sertraline at concentrations ranging from 15.625 to 500 µg/mL. Cell viability was measured using the MTT assay after 24 hours. The data were analyzed using ANOVA.

Results

Sertraline reduced PANC 1 cell viability in a dose-dependent manner: 500 µg/mL (≈10% viability), 250 µg/mL (≈25%), 125 µg/mL (≈40%), 62.5 µg/mL (≈50%), and 31.25 µg/mL (≈85% viability). No significant effect was observed at 15.625 µg/mL or in control samples.

Conclusions

These findings support the repositioning of sertraline as a novel psychoactive substance with anticancer properties. Its selective cytotoxicity toward PANC 1 cells highlights potential for therapeutic development in pancreatic cancer.
对新型抗癌疗法的研究导致了精神活性药物的重新定位。舍曲林是一种选择性5 -羟色胺再摄取抑制剂(SSRI),作为癌症治疗的候选药物已经超越了它的精神病学用途。目的:评价舍曲林对胰腺癌细胞(PANC - 1)的抗癌潜力,并评估其剂量依赖性的细胞毒作用。方法用15.625 ~ 500µg/mL浓度的舍曲林处理spanc 1细胞。24小时后用MTT法测定细胞活力。数据采用方差分析。结果舍曲林降低PANC - 1细胞活力呈剂量依赖性:500µg/mL(≈10%活力)、250µg/mL(≈25%)、125µg/mL(≈40%)、62.5µg/mL(≈50%)、31.25µg/mL(≈85%活力)。在15.625µg/mL或对照样品中未观察到显著影响。结论舍曲林是一种具有抗癌作用的新型精神活性物质。其对PANC - 1细胞的选择性细胞毒性突出了胰腺癌治疗发展的潜力。
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引用次数: 0
Investigating Naloxone's Efficacy in Reversing Cardiorespiratory Effects of Novel Synthetic Opioids 纳洛酮逆转新型合成阿片类药物心肺作用的疗效研究
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100197
S. Bilel

Introduction

Novel synthetic opioids (NSOs), represent a growing public health concern due to their high potency and association with increasing cases of intoxication and fatal overdose. They include fentanyl analogs, non-fentanyl compounds, and emerging classes such as benzimidazole opioids and nitazenes. Naloxone remains the primary treatment for opioid overdose. However, the efficacy of naloxone can vary depending on the pharmacokinetic and pharmacodynamic profiles of each compound. The aim of this study is to evaluate the role of naloxone pre-treatment in preventing cardio-respiratory impairment induced by a selection of NSOs, ranging from older to newly identified substances.

Methods

Male CD-1 mice were used to assess the acute cardiorespiratory effects of various NSOs. The tested compounds included MT-45 (15 mg/kg), fentanyl alone and with xylazine (1 mg/kg + 10 mg/kg), brorphine (15 mg/kg), etonitazene (0.3 mg/kg), and isotonitazene (0.3 mg/kg). To evaluate opioid receptor-mediated effects, naloxone (6 mg/kg, i.p.) was administered as a pre-treatment.

Results

All tested NSOs significantly reduced heart rate and respiratory rate in mice. The severity and reversibility of these effects varied across compound classes. Naloxone pre-treatment fully prevented the cardiorespiratory impairments of MT-45 but only partially the effects induced by all other opioids. Notably, nitazenes demonstrated the most potent and resistant profile to naloxone reversal.

Conclusions

These results underscore the high toxicity of NSOs, highlighting the need for Naloxone redosing in clinical settings.
新型合成阿片类药物(nso)由于其高效力和与日益增加的中毒和致命过量病例相关,引起了越来越多的公共卫生关注。它们包括芬太尼类似物、非芬太尼化合物和新兴类别,如苯并咪唑类阿片类药物和nitazene。纳洛酮仍然是阿片类药物过量的主要治疗方法。然而,纳洛酮的功效取决于每种化合物的药代动力学和药效学特征。本研究的目的是评估纳洛酮预处理在预防一系列nso(从旧的到新发现的物质)引起的心肺功能损害中的作用。方法采用小型CD-1小鼠,观察不同nso对急性心肺功能的影响。所测试的化合物包括MT-45 (15mg /kg)、芬太尼单独和与噻嗪(1mg /kg + 10mg /kg)、啡(15mg /kg)、依替硝唑(0.3 mg/kg)和异替硝唑(0.3 mg/kg)。为了评估阿片受体介导的作用,纳洛酮(6 mg/kg, i.p)作为预处理。结果所有nso均能显著降低小鼠心率和呼吸频率。这些影响的严重程度和可逆性因化合物类别而异。纳洛酮预处理可以完全预防MT-45的心肺功能损害,但只能部分预防其他阿片类药物引起的心肺功能损害。值得注意的是,nitazene表现出对纳洛酮逆转最有效和最耐药的特征。结论这些结果强调了nso的高毒性,强调了在临床环境中纳洛酮重新给药的必要性。
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引用次数: 0
“Emptiness Filled with Love”: A Reflexive Thematic Analysis of Chemsex Trajectories Among Gay, Bisexual, and Other Men Who Have Sex with Men in Almaty, Kazakhstan Using a Life Course Framework “充满爱的空虚”:利用生命历程框架对哈萨克斯坦阿拉木图同性恋、双性恋和其他与男性发生性行为的男性的化学性轨迹进行反思性主题分析
Pub Date : 2025-12-01 DOI: 10.1016/j.etdah.2025.100240
N. Lunchenkov, N. Cherchenko, E. German, S. Rinne-Wolf

Introduction

Chemsex (intentional psychoactive substance use to enhance sexual experiences) among gay, bisexual, and other men who have sex with men (GBMSM) is associated with HIV transmission and psychological distress. Limited research exists on chemsex trajectories in Eastern Europe and Central Asia, where structural homophobia and restrictive policies uniquely shape risks. This study identified chemsex engagement stages and examined how social, psychological, and structural factors influence transitions among GBMSM in Kazakhstan.

Methods

A cross-sectional qualitative study was conducted in Almaty, Kazakhstan (July-September 2023). Twenty-one GBMSM who engaged in chemsex within 12 months participated in 60-90 minute semi-structured interviews. All participants used mephedrone and/or alpha-PHP. Deductive reflexive thematic analysis, guided by Life Course Theory, reconstructed chemsex trajectories from retrospective accounts.

Results

Four trajectory stages emerged: Initiation occurred through trusted networks in intimate settings, fulfilling emotional needs for connection. Maintenance involved self-imposed limits but declining satisfaction with sober sex. Escalation featured breakdown of protective boundaries and increased use despite consequences. Dependence involved loss of control, with substance use shifting from pleasure enhancement to withdrawal coping. Structural stigma constrained agency throughout all stages, while chemsex networks provided emotional safety unavailable elsewhere.

Conclusions

Chemsex trajectories represent dynamic processes where substance use functions as emotional regulation and social survival strategies in high-stigma contexts, shaped by interactions between individual agency and structural constraints.
男同性恋、双性恋和其他男男性行为者(GBMSM)中的化学性行为(故意使用精神活性物质以增强性体验)与艾滋病毒传播和心理困扰有关。关于东欧和中亚的化学性行为轨迹的研究有限,在那里,结构性的同性恋恐惧症和限制性政策独特地形成了风险。本研究确定了化学性接触阶段,并考察了社会、心理和结构因素如何影响哈萨克斯坦GBMSM的转变。方法于2023年7 - 9月在哈萨克斯坦阿拉木图进行横断面定性研究。21名在12个月内从事化学性行为的GBMSM参加了60-90分钟的半结构化访谈。所有参与者使用甲氧麻黄酮和/或alpha-PHP。在生命历程理论的指导下,演绎反身性主题分析从回顾性的叙述中重建了化学性轨迹。结果:初始化发生在亲密环境下的信任网络中,满足情感需求。维持包括自我强加的限制,但对清醒的性行为的满意度下降。升级的特点是破坏保护边界,不顾后果地增加使用。依赖包括失去控制,物质使用从增强快感转变为戒断应对。结构性的耻辱感在所有阶段都限制了代理,而化学性网络提供了其他地方无法获得的情感安全。结论图式性别轨迹反映了高污名情境下物质使用作为情绪调节和社会生存策略的动态过程,这一过程受个体能动性和结构约束的相互作用影响。
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Emerging trends in drugs, addictions, and health
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