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目的：考察甲卡西酮(Methcathinone)、3-(2-羧基乙基)胞嘧啶(3-(2-carboxyethyl)cytosine,3-CEC)、1-(4-甲基苯基)-2-(甲氨基)-3-甲氧基-1-丙酮(3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one,Mexedrone)、1-(1,3-苯并二茂-5-基)-2-丙基氨基-1-丙酮(3,4-Methylenedioxy-N-propylcathinone,Propylone)、1-[3,4-(亚甲二氧基苯基)]-2-甲氨基-1-戊酮(1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one,Pentylone)和4-氯-α-(N-吡咯烷基)苯戊酮(4-chloro-α-pyrrolidinovalerophenone,4-Cl-α-PVP)的血脑屏障通透性及体外代谢清除率。方法：利用hCMECD3细胞单层模型，通过LC-MS/MS分析方法测定6种合成卡西酮类毒品的跨膜转运浓度，并计算其表观渗透系数(Papp)，同时，通过人肝微粒体体外代谢模型获得6种合成卡西酮类物质的体外代谢清除率，并根据体内外的比放系数(scaling factor,SF)求得相应体内清除率。结果：在细胞转运90 min时，5种合成卡西酮类新型毒品的Papp值均低于甲卡西酮，顺序为甲卡西酮(4.51×10-5 cm/s)>Pentylone(3.48×10-5 cm/s)>Propylone(3.33×10-5 cm/s)>mexedrone(3.15×10-5 cm/s)>3-CEC(3.00×10-5 cm/s)>4-Cl-α-PVP(1.92×10-5 cm/s)；体外代谢清除率顺序为Mexedrone(0.0024 ml/min·mg)<甲卡西酮(0.0041 ml/min·mg)
Objective: To examine Methcathinone, 3-(2-carboxyethyl)cytosine(3-CEC), 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one(Mexedrone), 3, 4-Methylenedioxy-N-propylcathinone(Propylone), 1-(1, 3-benzodioxol-5-yl)-2-(methylamino) pentan-1-one(Pentylone) and 4-chloro-α-pyrrolidinovalerophenone(4-Cl-α-PVP) in terms of blood-brain barrier permeability and in vitro metabolic clearance. Methods: The transmembrane transport concentrations of the six synthetic cathinones were assessed via LC-MS/MS analysis utilizing the hCMECD3 cell monolayer model, and their apparent permeability coefficients(Papp) were computed. Simultaneously, the in vitro metabolic clearances of the six synthetic cathinones were determined using a human liver microsome metabolism model, and the corresponding in vivo clearance rates were derived based on the scaling factor(SF) between in vivo and in vitro. Results: After 90 minutes of cellular transit, the Papp values for the five novel synthetic cathinones were lower than to that of Methcathinone, ranked as follows: Methcathinone(4.51×10-5 cm/s) > Pentylone(3.48×10-5 cm/s) > Propylone(3.33×10-5 cm/s) > Mexedrone(3.15×10-5 cm/s) > 3-CEC(3.00×10-5 cm/s) > 4-Cl-α-PVP(1.92×10-5 cm/s); The sequence of in vitro metabolic clearance was as follows: Mexedrone(0.0024 ml/min·mg) < Methcathinone(0.0041 ml/min·mg) < Pentylone(0.0075 ml/min·mg) < 3-CEC(0.0091 ml/min·mg) < 4-Cl-α-PVP(0.0170 ml/min·mg) < Propylone(0.0240 ml/min·mg). Conclusion: All six synthetic cathinones show favorable permeability in an in vitro blood-brain barrier model. Except for 4-Cl-α-PVP, which shows intermediate permeability(thresholds 5～20 × 10-6 cm/s), several other compounds display high permeability(thresholds >20 × 10-6 cm/s). Furthermore, the intrinsic clearances(CLint) of the six synthetic cathinones are less than 0.1 ml/min·mg, with Mexedrone showing the lowest CLint of 0.0024 ml/min·mg, indicating significant metabolic stability. These data demonstrate that the six synthetic cathinones exhibit significant central nervous system toxicity and potential for accumulating toxicity, thereby increasing the risk of acute intoxication due to over abuse.
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基本信息:
DOI：10.15900/j.cnki.zylf1995.2025.11.005
中图分类号:R99
引用信息:
[1]杨洋,赵晓媛,刘文娟,等.合成卡西酮类毒品血脑屏障通透性及体外代谢清除率的比较研究[J].中国药物滥用防治杂志,2025,31(11):1975-1979+1983.DOI:10.15900/j.cnki.zylf1995.2025.11.005.
基金信息:
毒品监测管控与禁毒关键技术公安部重点实验室开放基金（编号：2023-KLDMC-06）; 江苏高校“青蓝工程”人才项目资助
2025-02-25
2025
2026-03-04
2026
2
2025-11-15
2025-11-15