亚甲基二氧基甲卡西酮 | 186028-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: 亚甲基二氧基甲卡西酮
• 中文别名: 2-甲基氨基-1-(3,4-亚甲二氧苯基)-1-丙酮；敏疫朗
• 英文名称: methylone
• 英文别名: 3,4-methylenedioxy-N-methylcathinone；1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one；3,4-methylenedioxymethcathinone；3,4-methylendioxymethcathinone
• CAS: 186028-79-5
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: VKEQBMCRQDSRET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

近年来，在许多国家的滥用药物市场上出现了一种新型设计药物，即所谓的β-酮（bk）设计药物，例如甲氧基苯丙酮（bk-4-甲基甲基安非他明）、丁酮（bk-MBDB）和甲基酮（bk-MDMA）。本研究的目的是使用GC-MS技术识别大鼠和人类尿液中甲氧基苯丙酮的代谢物，并将甲氧基苯丙酮、丁酮和甲基酮纳入作者的系统性毒理分析（STA）程序。在大鼠尿液中检测到六种甲氧基苯丙酮的一相代谢物，在人类尿液中检测到七种，表明以下代谢步骤：N-脱甲基形成一级胺，将酮基还原为相应的醇，以及对甲苯基的氧化形成相应的醇和羧酸。STA程序允许在大鼠尿液中检测到甲氧基苯丙酮、丁酮、甲基酮及其代谢物，这些大鼠接受的剂量与报告的滥用安非他命的剂量相当。除了基于宏观数据评估外，还使用自动质量谱分解和识别系统进行了自动评估。甲氧基苯丙酮和丁酮也可以在提交药物测试的人类尿液中检测到。假设人类具有相似的动力学，所描述的STA程序应适用于证明人类尿液中摄入了bk设计药物。

In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors' systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲基酮在人和大鼠体内的尿代谢物通过分析滥用者的尿液样本以及用气相色谱-质谱（GC-MS）和液相色谱-电喷雾电离质谱（LC-ESI MS）对大鼠给药后来进行研究，使用真实标准。在大鼠单次腹腔注射5 mg/kg甲基酮盐酸盐后，进一步研究了甲基酮及其三种代谢物在大鼠体内的排泄时间过程。揭示了人和大鼠的两个主要代谢途径如下：(1) 通过N-去甲基化到相应的一级胺甲氧基环己酮（MDC），部分发生共轭反应；和(2) 去甲基化后，在苯环上O-甲基化3-或4-OH基团，分别产生4-羟基-3-甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基甲氧基

The urinary metabolites of methylone in humans and rats were investigated by analysing urine specimens from its abuser and after administrating to rats with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards. The time-course excretion profiles of methylone and its three metabolites in rats were further investigated after a single intraperitoneal dosing of 5 mg/ kg methylone hydrochloride. Two major metabolic pathways were revealed for both humans and rats as follows: (1) side-chain degradation by N-demethylation to the corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these metabolites, HMMC was the most abundant in humans and rats. The cumulative amount of urinary HMMC excreted within the first 48 hr in rats was approximately 26% of the dose, and the amount of the parent methylone was not more than 3%. These results demonstrate that the analysis of HMMC will be indispensable for proof of the use of methylone in forensic urinalysis.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

迹象和症状：甲基酮自述副作用 [表#7950]

/SIGNS AND SYMPTOMS/ Self Reported Side Effects of Methylone [Table#7950]

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

病例报告：本报告介绍了一个与服用甲基酮有关的致命案例，甲基酮是一种相对较新的卡西酮类设计药物。一名16岁男孩在派对中突然失去意识。在重症监护室进行了大约1.5小时的复苏尝试，但未能成功。他的既往病史包括在婴儿期发现的心脏畸形，以及在他去世前一年被诊断出的支气管哮喘。尸检时观察到猝死心脏的迹象。通过气相色谱/质谱法在血液和肝脏提取物中证实了甲基酮的摄入；血液中的浓度为272 ng/mL，肝脏中的浓度为387 ng/g。病理学检查显示肝脏有微血管脂肪变性，这提高了长期使用有毒物质的可能性。此外，还观察到了条纹状心肌损伤，这可能是由于使用了类似安非他明的物质。...

/CASE REPORTS/ This report presents a fatal case related to the consumption of methylone, a relatively new cathinone type designer drug. A 16-year-old boy suddenly lost his consciousness in a party. Resuscitation had been continued for about 1.5 hr at the intensive care unit, but it was unsuccessful. His previous history included cardiac malformation detected at infancy and bronchial asthma had been diagnosed one year before his death. Signs of sudden cardiac death were observed during autopsy. Methylone intake was proved in blood and liver extract using gas chromatography/mass spectrometry; its concentration was 272 ng/mL in the blood, and 387 ng/g in the liver. Pathohistology revealed microvascular steatosis in the liver, which raised the possibility of chronic use of toxic substances. In addition, striated heart muscle damage was observed, which could be due to the use of an amphetamine-like substance. ...

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

医药中间体。

用途简介

反应信息

• 作为反应物：
  描述：

  亚甲基二氧基甲卡西酮 在 盐酸 作用下， 以 乙醚 为溶剂， 以94 %的产率得到2-甲基氨基-1-(3,4-亚甲二氧苯基)-1-丙酮盐酸盐
  参考文献：
  名称：

  [EN] ISOTOPOLOGES, SALTS, CRYSTALLINE FORMS, STEREOISOMERS, OF METHYLONE AND ETHYLONE AND METHODS OF USE THEREOF
  [FR] ISOTOPOLOGUES, SELS, FORMES CRISTALLINES, STÉRÉOISOMÈRES, DE MÉTHYLONE ET D'ÉTHYLONE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  Described herein are isotopically enriched analogs of methylone (e.g., deuterated analogs of methylone (e.g., (S)-methylone and (R)-methylone) with improved characteristics. Also described herein are salts (such as hydrochloride salt) and solid forms (e.g., crystalline forms) of methylone. Also described herein are stereoisomers (e.g., enantiomers) of methylone. The present disclosure also provides methods of making and methods of use of the methylone or methylone analogs and solid forms of 3,4-methylenedioxy-N-ethylcathinone hydrochloride described herein to treat brain and neurological disorders such as depression.

  公开号：

  WO2023081403A1
• 作为产物：
  描述：

  胡椒环 在 aluminum (III) chloride 、 溴 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 亚甲基二氧基甲卡西酮
  参考文献：
  名称：

  用于抑制AChE / BChE的新型基于苯甲酸酯的氨基甲酸酯：合成和面向配体/结构的SAR研究

  摘要：

  设计，合成和全面表征了一系列新的苯基衍生物。对所有测试化合物的体外抑制潜在的乙酰基和丁酰胆碱酯酶的能力进行了评估。还确定了单个分子对胆碱酯酶的选择性指数。通常，与乙酰胆碱酯酶相比，对丁酰的抑制作用更强。然而，某些化合物对这两种酶均显示出有希望的抑制作用。实际上，有两种化合物（23，（1-氧代-1-苯基丙-2-基氨基甲酸苄基乙基氨基甲酸酯和28，（1-（3-氯代苯基）-1-氧代丙-2-基）氨基甲酸苄基酯（28））具有很高的选择性指数，而第二个（28）达到最低的抑制浓度IC50值，与加兰他敏相当好。而且，进行了与受体无关和受体依赖的结构活性比较研究，以解释观察到的抑制氨基甲酸酯系列潜力的变化。基于配体的研究的主要目的是比较分析分子表面，以深入了解控制酶活性抑制能力的电子和/或位阻因素。潜在重要的空间和静电因子的空间分布是使用基于概率变量的药效团作图程序确定的，该程序基于迭代变量消除方法。此外，

  DOI：

  10.3390/ijms20071524

文献信息

• Successful use of a novel lux® i‐Amylose‐1 chiral column for enantioseparation of “legal highs” by HPLC
  作者：Kian Kadkhodaei、Marlene Kadisch、Martin G. Schmid

  DOI：10.1002/chir.23135

  日期：2020.1

  enantiomers may differ in their pharmacological effect. The aim of this study was to test a novel HPLC column for the enantioseparation of a set of 112 NPS coming from different chemical groups and collected by internet purchases during the years 2010–2018. The CSP, namely Lux® 5 μm i‐Amylose‐1, LC Column 250 x 4.6 mm, was run in normal phase mode under isocratic conditions, UV detection was performed

  这些术语背后隐藏着浴盐，熏蒸剂，清洁剂和空气清新剂，这些物质被算作“合法上限”。这些花哨的名字被用来装扮成合法的无害化合物，以规避市场营销的法律法规并增加销量。除了合成的经典非法药物（如苯丙胺，可卡因和摇头丸）以外，这些化合物的贸易（也称为新型精神活性物质（NPS））在当今并不罕见。在许多国家，NPS仍然不受药物管制。其中，有具有手性中心的兴奋剂，例如新的苯丙胺衍生物或卡西酮。关于两种可能的对映异构体的药理作用可能不同的事实知之甚少。这项研究的目的是测试一种新颖的HPLC色谱柱，该色谱柱用于对映分离2010年至2018年间通过互联网购买的来自不同化学族的112种NPS。CSP，即Lux®5μmi-Amylose-1，LC色谱柱250 x 4.6 mm，在等度条件下以正相模式运行，在245 nm和230 nm处进行UV检测，进样量为10μl，流速为为1毫升/分钟。使用由正己烷/异丙醇/二乙胺（90：10：0
• IMMUNOASSAY FOR PYRROLIDINOPHENONES
  申请人：RANDOX LABORATORIES LIMITED

  公开号：US20160097783A1

  公开（公告）日：2016-04-07

  The current invention provides an improved immunoassay for the detection and determination of pyrrolidinophenone based designer drugs in hair and biological fluids (urine, blood, and oral fluid). The generic immunoassay is underpinned by novel, sub-family-specific antibodies, which display surprising sensitivity. The invention further describes substrates comprising an antibody that is specific to compounds of the pyrrolidinophenone family. Also described are the novel immunogens from which the antibodies are derived and kits incorporating the antibodies of the current invention.

  该发明提供了一种改进的免疫测定方法，用于检测和测定基于哌哆利啶酮类设计药物在头发和生物液体（尿液、血液和口腔液）中的含量。通用的免疫测定方法基于新颖的、亚家族特异性抗体，显示出惊人的灵敏度。该发明进一步描述了包含特异于哌哆利啶酮类化合物的抗体的底物。还描述了从中获得抗体的新颖免疫原以及包含本发明抗体的试剂盒。
• In Vitro Metabolism and Pharmacokinetic Studies on Methylone
  作者：Anders Just Pedersen、Trine Hedebrink Petersen、Kristian Linnet

  DOI：10.1124/dmd.112.050880

  日期：2013.6

  Abuse of the stimulant designer drug methylone (methylenedioxymethcathinone) has been documented in most parts of the world. As with many of the new designer drugs that continuously appear in the illicit drug market, little is known about the pharmacokinetics of methylone. Using in vitro studies, CYP2D6 was determined to be the primary enzyme that metabolizes methylone, with minor contributions from CYP1A2, CYP2B6, and CYP2C19. The major metabolite was identified as dihydroxymethcathinone, and the minor metabolites were N -hydroxy-methylone, nor-methylone, and dihydro-methylone. Measuring the formation of the major metabolite, biphasic Michaelis–Menten kinetic parameters were determined: V max,1 = 0.046 ± 0.005 (S.E.) nmol/min/mg protein, K m,1 = 19.0 ± 4.2 μ M, V max,2 = 0.22 ± 0.04 nmol/min/mg protein, and K m,2 = 1953 ± 761 μ M; the low-capacity and high-affinity contribution was assigned to the activity of CYP2D6. Additionally, a time-dependent loss of CYP2D6 activity was observed when the enzyme was preincubated with methylone, reaching a maximum rate of inactivation at high methylone concentrations, indicating that methylone is a mechanism-based inhibitor of CYP2D6. The inactivation parameters were determined to be K I = 15.1 ± 3.4 (S.E.) μ M and k inact = 0.075 ± 0.005 minute−1.

  世界大部分地区都有滥用兴奋剂特制药物甲酮（亚甲二氧基甲卡西酮）的记录。与非法药物市场上不断出现的许多新型特制药物一样，人们对甲酮的药代动力学知之甚少。通过体外研究，确定 CYP2D6 是代谢甲酮的主要酶，CYP1A2、CYP2B6 和 CYP2C19 对其代谢作用较小。主要代谢物被确定为二羟基甲卡西酮，次要代谢物为 N -羟基甲酮、去甲甲酮和二氢甲酮。通过测定主要代谢物的形成过程，确定了双相迈克尔-门顿动力学参数：V max,1 = 0.046 ± 0.005 (S.E.) nmol/min/mg 蛋白质，K m,1 = 19.0 ± 4.2 μ M，V max,2 = 0.22 ± 0.04 nmol/min/mg 蛋白质，K m,2 = 1953 ± 761 μ M；低能力和高亲和力的贡献归因于 CYP2D6 的活性。此外，当 CYP2D6 与甲缩醛预孵育时，观察到 CYP2D6 活性的丧失与时间有关，在高浓度甲缩醛时达到最大失活率，这表明甲缩醛是一种基于机制的 CYP2D6 抑制剂。灭活参数被确定为 K I = 15.1 ± 3.4 (S.E.) μ M 和 k inact = 0.075 ± 0.005 minute-1。
• Enantioselectivity of Pentedrone and Methylone on Metabolic Profiling in 2D and 3D Human Hepatocyte-like Cells
  作者：Bárbara Silva、Joana Saraiva Rodrigues、Ana Sofia Almeida、Ana Rita Lima、Carla Fernandes、Paula Guedes de Pinho、Joana Paiva Miranda、Fernando Remião

  DOI：10.3390/ph15030368

  日期：——

  Pentedrone and methylone can express stereoselectivity in toxicokinetic and toxicodynamic processes. Similarly, their chiral discrimination in metabolism, which was not yet evaluated, can result in different metabolic profiles and subsequent hepatotoxic effects. Therefore, the aim of this work was to assess, for the first time, both the hepatic cytotoxic and metabolic profile of pentedrone and methylone enantiomers using physiologically relevant in vitro models. The hepatotoxicity of these compounds was observed in a concentration-dependent manner in human stem-cell-derived hepatocyte-like cells (HLCs) cultured under 3D (3D-HLCs) and 2D (2D-HLCs) conditions. Enantioselectivity, on the other hand, was only shown for pentedrone (1 mM) in 3D-HLCs, being R-(−)-pentedrone the most cytotoxic. Furthermore, the metabolic profile was initially evaluated in human liver microsomes (HLM) and further demonstrated in 3D-HLCs and 2D-HLCs applying a gas chromatography coupled to a mass spectrometer (GC–MS) technique. Methylone and pentedrone showed distinct and preferential metabolic routes for their enantiomers, resulting in the production of differentiated metabolites; R-(+)-methylone and R-(−)-pentedrone are the most metabolized enantiomers. In conclusion, the results demonstrated enantioselectivity for pentedrone and methylone in the metabolic processes, with enantioselectivity in cytotoxicity for pentedrone.

  喷脱酮和甲酮在毒代动力学和毒效学过程中具有立体选择性。同样，它们在代谢过程中的手性鉴别（尚未进行评估）也会导致不同的代谢特征和随后的肝毒性效应。因此，这项工作的目的是利用生理相关的体外模型，首次评估喷脱酮和甲酮对映体的肝细胞毒性和代谢特征。在三维（3D-HLCs）和二维（2D-HLCs）条件下培养的人干细胞衍生肝细胞样细胞（HLCs）中，以浓度依赖性方式观察到了这些化合物的肝毒性。另一方面，在三维-HLCs中，只有pentedrone（1 mM）显示出对映选择性，R-(-)-pentedrone的细胞毒性最强。此外，还在人类肝脏微粒体（HLM）中对代谢概况进行了初步评估，并采用气相色谱-质谱联用仪（GC-MS）技术在三维液相色谱和二维液相色谱中进行了进一步验证。甲酮和喷脱酮显示出其对映体不同的优先代谢途径，从而产生了不同的代谢产物；R-(+)-甲酮和 R-(-)-喷脱酮是代谢最多的对映体。总之，研究结果表明五酮和甲酮在代谢过程中具有对映体选择性，五酮在细胞毒性方面具有对映体选择性。
• Iwao et al., Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1954, vol. 74, p. 551,553
  作者：Iwao et al.

  DOI：——

  日期：——