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氯胺酮类似物研究进展*

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  • 1.中国人民公安大学侦查学院,北京 100038;
    2.公安部物证鉴定中心,北京 100038
第一作者 Tel:17854129216;E-mail:liukexin970906@icloud.com
** 董林沛 Tel:15711123667;E-mail:461026507@qq.com
姜 红 Tel:15611315448;E-mail:jiangh2001@163.com

收稿日期: 2021-10-19

  网络出版日期: 2024-06-24

基金资助

* 中央级公益性科研院所基本科研业务费(2021JB007)

Research progress of ketamine analogues*

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  • 1. School of Investigation, People’s Public Security University of China, Beijing 100038, China;
    2. Institute of Forensic Science, Ministry of Public Security, Beijing 100038

Received date: 2021-10-19

  Online published: 2024-06-24

摘要

近年来,包含氯胺酮类似物在内的新精神活性物质不断涌现,在世界范围内引起严重的卫生问题和社会问题。氯胺酮类似物以芳基环乙胺为母核,通过有针对性的结构修饰,达到与氯胺酮相似甚至更强劲的生理反应。过量服用氯胺酮类似物而导致急性死亡的案例被广泛报道,为了快速精准地控制和打击该类物质的滥用和犯罪,各国根据实际情况开发了各种筛查与定性定量方法。本文对氯胺酮类似物的化学结构、毒理学性质、中毒案例及近年来生物检材中的检测方法进行总结,并对氯胺酮类似物的毒理学研究提出了展望。

本文引用格式

刘克新, 任昕昕, 董林沛, 姜红, 王瑞花 . 氯胺酮类似物研究进展*[J]. 药物分析杂志, 2022 , 42(5) : 735 -747 . DOI: 10.16155/j.0254-1793.2022.05.01

Abstract

In recent years, the boom of new psychoactive drugs including ketamine analogues, has caused serious hygienic and social problems worldwide. Due to its structure of arylcycloethylamine as a mother nucleus structure and modification of targeted functional group, ketamine analogues own similar or even stronger physiological reaction to drug abuser, compared to its prototype ketamine. Thus, cases of acute death involved to overdose of ketamine analogues have been widely reported. Various quick and accurate methods for screening or qualitative and quantitative analysis were established widely throughout the world to fight against the abuse of these substances and related crime.In this review, the chemical structure, toxicological properties, poisoning cases and some novel detection methods of ketamine analogues were summarized, and the prospect of toxicological research on ketamine analogues was represent.

参考文献

[1] FAGIOLA M, HAHN T, AVELLA J. Screening of novel psychoactive substances in postmortem matrices by liquid chromatography-tandem mass spectrometry (LC-MS-MS)[J].J Anal Toxicol, 2018, 42(8):562
[2] NAMERA A, KAWAMURA M, NAKAMOTO A, et al. Comprehensive review of the detection methods for synthetic cannabinoids and cathinones[J].Forensic Toxicol, 2015, 33(2):175
[3] The United Nations Office on Drugs and Crime. DATA FROM THE UNODC EARLY WARNING ADVISORY ON NEW PSYCHOACTIVE SUBSTANCES[EB/OL].(2021-08-26)[2021-08-29]. https://www.unodc.org/unodc/en/scientists/ewa/data.html
[4] TANG MHY, LI TC, LAI CK, et al. Emergence of new psychoactive substance 2-fluorodeschloroketamine: toxicology and urinary analysis in a cluster of patients exposed to ketamine and multiple analogues[J].Forensic Sci Int, 2020, 312:110327
[5] CHENG WC, DAO KL. The emergence of deschloro-N-ethyl-ketamine, a ketamine analog, in drug seizures and drug driving cases in Hong Kong[J].J Anal Toxicol, 2020, 44(8):886
[6] MENZIES EL, HUDSON SC, DARGAN PI, et al. Characterizing metabolites and potential metabolic pathways for the novel psychoactive substance methoxetamine[J].Drug Test Anal, 2014, 6(6):506
[7] TANG MHY, CHONG YK, CHAN CY, et al. Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE[J].Forensic Sci Int, 2018, 290:238
[8] CHIAPPINI S, CLARIDGE H, CORKERY JM, et al. Methoxetamine-related deaths in the UK:an overview[J].Human Psychopharmacol Clin Exp, 2015, 30(4):244
[9] ADAMOWICZ P, ZUBA D. Fatal intoxication with methoxetamine[J].J Forensic Sci, 2015, 60:S264
[10] European Monitoring Centre for Drugs and Drug Addiction and EUROPOL. EU Drug Markets Report:a strategic analysis[R].Lisbon, 2013
[11] ZAWILSKA JB. Methoxetamine-a novel recreational drug with potent hallucinogenic properties[J].Toxicol Lett, 2014, 230(3):402
[12] GOMILA I, LECIÑENA MÁ, ELORZA MÁ, et al. Detectability of dissociative psychoactive substances in urine by five commercial phencyclidine immunoassays[J].J Anal Toxicol, 2019, 43(6):497
[13] CHENG WJ, CHEN CH, CHEN CK, et al. Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia[J].Schizophr Res, 2018, 199:313
[14] WIKSTRÖM M, THELANDER G, DAHLGREN M, et al. An accidental fatal intoxication with methoxetamine[J].J Anal Toxicol, 2013, 37(1):43
[15] ZANDA MT, FADDA P, CHIAMULERA C, et al. Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects:a review of case reports and preclinical findings[J].Behav Pharmacol, 2016, 27(6):489
[16] DAVIDSEN AB, MARDAL M, HOLM NB, et al. Ketamine analogues:comparative toxicokinetic in vitro-in vivo extrapolation and quantification of 2-fluorodeschloroketamine in forensic blood and hair samples[J].J Pharm Biomed Anal, 2020, 180:113049
[17] CELIA JA, MORGAN H,VALERIE, et al. Ketamine use:a review[J].Addiction,2012,107(1):27
[18] HÁJKOVÁ K, JURÁSEK B, EJKA J, et al. Synthesis and identification of deschloroketamine metabolites in rats’ urine and a quantification method for deschloroketamine and metabolites in rats’ serum and brain tissue using liquid chromatography tandem mass spectrometry[J].Drug Test Anal, 2020, 12(3):343
[19] ACEVEDO-DIAZ EE, CAVANAUGH GW, GREENSTEIN D, et al. Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression[J].J Affective Disord, 2020, 263:568
[20] MORRIS H, WALLACH J. From PCP to MXE:a comprehensive review of the non-medical use of dissociative drugs[J].Drug Test Anal, 2014, 6(7-8):614
[21] ZANOS P, MOADDEL R, MORRIS P J, et al. Ketamine and ketamine metabolite pharmacology:insights into therapeutic mechanisms[J].Pharmacol Rev, 2018, 70(3):621
[22] COSTA G, SERRA M, PINTORI N, et al. The novel psychoactive substance methoxetamine induces persistent behavioral abnormalities and neurotoxicity in rats[J].Neuropharmacology, 2019, 144:219
[23] KASHIWAZAKI M, NODA K. Effect of ketamine on the excitability of peripheral nerves[J].Masui, 1998, 47(6):696
[24] MORGAN CJA, REES H, CURRAN HV. Attentional bias to incentive stimuli in frequent ketamine users[J].Psychol Med, 2008, 38(9):1331
[25] BOTANAS CJ, DE LA PEÑA JB, DELA PENA IJ, et al. Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: evidence of its abuse potential[J].Pharmacol Biochem Behav, 2015, 133:31
[26] Articles about Erowid Experience Reports[EB/OL].[2021-08-15]. https://erowid.org/experiences/
[27] MEYER MR, VOLLMAR C, SCHWANINGER AE, et al. New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine[J].J Mass Spectrom, 2012, 47(2):253
[28] HORSLEY RR, LHOTKOVA E, HAJKOVA K, et al. Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue-behavioural, pharmacokinetic and metabolic studies in the Wistar rat[J].Brain Res Bull, 2016, 126:102
[29] BEY T, PATEL A. Phencyclidine intoxication and adverse effects:a clinical and pharmacological review of an illicit drug[J].Calif J Emerg Med, 2007, 8(1):9
[30] SKAUGEN JM, SCOCCIMARRO A, PIZON AF, et al. Novel ketamine analogues cause a false positive phencyclidine immunoassay[J].Ann Clin Biochem, 2019, 56(5):598
[31] LIU CH, WANG HY, SHEN SH, et al. False positive ketamine urine immunoassay screen result induced by quetiapine:a case report[J].J Formos Med Assoc, 2017, 116(9):720
[32] DE PAOLI G, BRANDT SD, WALLACH J, et al. From the street to the laboratory:analytical profiles of methoxetamine, 3-methoxyeticyclidine and 3-methoxyphencyclidine and their determination in three biological matrices[J].J Anal Toxicol, 2013, 37(5):277
[33] THEOFEL N, MÖLLER P, VEJMELKA E, et al. A fatal case involving N-ethyldeschloroketamine (2-oxo-PCE) and venlafaxine[J].J Anal Toxicol, 2019, 43(2):e2
[34] LEHMANN S, SCHULZE B, THOMAS A, et al. Organ distribution of 4-MEC, MDPV, methoxetamine and α-PVP:comparison of QuEChERS and SPE[J].Forensic Toxicol, 2018, 36(2):320
[35] LEHMANN S, KIELIBA T, BEIKE J, et al. Determination of 74 new psychoactive substances in serum using automated in-line solid-phase extraction-liquid chromatography-tandem mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci, 2017, 1064:124
[36] ANASTASSIADES M, LEHOTAY SJ, TAJNBAHER D, et al. Fast and easy multiresidue method employing acetonitrile extraction/partitioning and “dispersive solid-phase extraction” for the determination of pesticide residues in produce[J].J AOAC Int, 2003, 86(2):412
[37] WU H, ZHANG J, NOREM K, et al. Simultaneous determination of a hydrophobic drug candidate and its metabolite in human plasma with salting-out assisted liquid/liquid extraction using a mass spectrometry friendly salt[J].J Pharm Biomed Anal, 2008, 48(4):1243
[38] HAJKOVA K, JURASEK B, SYKORA D, et al. Salting-out-assisted liquid-liquid extraction as a suitable approach for determination of methoxetamine in large sets of tissue samples[J].Anal Bioanal Chem, 2016, 408(4):1171
[39] MIYAGUCHI H, KAKUTA M, IWATA YT, et al. Development of a micropulverized extraction method for rapid toxicological analysis of methamphetamine in hair[J].J Chromatogr A, 2007, 1163(1-2):43
[40] MIYAGUCHI H, INOUE H. Determination of amphetamine-type stimulants, cocaine and ketamine in human hair by liquid chromatography/linear ion trap-orbitrap hybrid mass spectrometry[J].Analyst, 2011, 136(17):3503
[41] FAVRETTO D, VOGLIARDI S, STOCCHERO G, et al. Determination of ketamine and norketamine in hair by micropulverized extraction and liquid chromatography-high resolution mass spectrometry[J].Forensic Sci Int, 2013, 226(1-3):88
[42] WOOD DM, DAVIES S, PUCHNAREWICZ M, et al. Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine[J].Eur J Clin Pharmacol, 2012, 68(5):853
[43] FRISON G, ZAMENGO L, ZANCANARO F, et al. Characterization of the designer drug deschloroketamine (2-methylamino-2-phenylcyclohexanone) by gas chromatography/mass spectrometry, liquid chromatography/high-resolution mass spectrometry, multistage mass spectrometry, and nuclear magnetic resonance[J].Rapid Commun Mass Spectrom, 2016, 30(1):151
[44] IMBERT L, BOUCHER A, DELHOME G, et al. Analytical findings of an acute intoxication after inhalation of methoxetamine[J].J Anal Toxicol, 2014, 38(7):410
[45] GICQUEL T, RICHEVAL C, MESLI V, et al. Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE)[J].Forensic Sci Int, 2021:110852
[46] TANG MHY, CHING CK, LEE CYW, et al. Simultaneous detection of 93 conventional and emerging drugs of abuse and their metabolites in urine by UHPLC-MS/MS[J].J Chromatogr B Analyt Technol Biomed Life Sci, 2014, 969:272
[47] SO PK, NG TT, WANG H, et al. Rapid detection and quantitation of ketamine and norketamine in urine and oral fluid by wooden-tip electrospray ionization mass spectrometry[J].Analyst, 2013, 138(8):2239
[48] WIERGOWSKI M, ANAND JS, KRZYPZANOWSKI M, et al. Acute methoxetamine and amphetamine poisoning with fatal outcome:a case report[J].Int J Occup Med Environ Health, 2014, 27(4):683
[49] FASSETTE T, MARTINEZ A. An impaired driver found to be under the influence of methoxetamine[J].J Anal Toxicol, 2016, 40(8):700
[50] ABE E, RICARD F, DARROUZAIN F, et al. An automated method for measurement of methoxetamine in human plasma by use of turbulent flow on-line extraction coupled with liquid chromatography and mass spectrometric detection[J].Anal Bioanal Chem, 2013, 405(1):239
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