Fujita Yuji, Mita Toshinori, Usui Kiyotaka, Kamijo Yoshito, Kikuchi Satoshi, Onodera Makoto, Fujino Yasuhisa, Inoue Yoshihiro
Division of Emergency Medicine, Department of Emergency, Disaster and General Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan.
Poisoning and Drug Laboratory Division, Critical Care and Emergency Center, Iwate Medical University Hospital, Morioka, Iwate, Japan.
J Anal Toxicol. 2018 Jan 1;42(1):e1-e5. doi: 10.1093/jat/bkx080.
Synthetic cathinones inhibit monoamine transporters, such as serotonin, norepinephrine, and dopamine transporters, and act on the central nervous system via increasing synaptic concentrations of monoamines. These compounds, which are highly addictive and potentially poisonous, are new psychoactive substances. In this study, we investigated the toxicokinetics of the synthetic cathinone, α-pyrrolidinohexanophenone (α-PHP), and assessed the relationship between the toxicokinetics and the long-term clinical symptoms induced by α-PHP in a male patient. The patient (39 years old) suddenly started uttering inarticulate words and demonstrating incomprehensible behavior in his house, and was brought to the emergency department of Iwate Medical University hospital. He presented with psychotic symptoms, such as hallucinations and delusion; however, his vital signs were normal. The hallucinations and delusion improved by the third day of hospitalization. Toxicological analysis was performed using liquid chromatography-tandem mass spectrometry with QuEChERS extraction. α-PHP was detected in his serum at a concentration of 175 ng/mL on his arrival at the hospital. His serum concentrations of α-PHP were serially determined and their natural logarithms were plotted against time after arrival. Although serum concentrations at early time points were lacking, the obtained curve was consistent with a two-compartment model and indicated a serum elimination half-life of 37 h. The long-lasting psychotic symptoms induced by synthetic cathinones appear to be correlated with their toxicokinetic characteristics, such as their long half-lives. Finally, interpreting the toxicokinetics of synthetic cathinones may provide useful information for the toxicological assessment of new psychoactive substances for forensic and clinical purposes.
合成卡西酮可抑制单胺转运体,如5-羟色胺、去甲肾上腺素和多巴胺转运体,并通过增加单胺的突触浓度作用于中枢神经系统。这些化合物极易成瘾且有潜在毒性,属于新型精神活性物质。在本研究中,我们调查了合成卡西酮α-吡咯烷基己酮(α-PHP)的毒代动力学,并评估了一名男性患者中α-PHP的毒代动力学与长期临床症状之间的关系。该患者(39岁)突然开始在其家中含糊不清地说话并表现出难以理解的行为,随后被送往岩手医科大学医院急诊科。他出现了幻觉和妄想等精神病症状;然而,其生命体征正常。住院第三天幻觉和妄想症状有所改善。采用QuEChERS萃取的液相色谱-串联质谱法进行毒理学分析。患者入院时血清中检测到α-PHP,浓度为175 ng/mL。连续测定其血清中α-PHP的浓度,并将其自然对数与入院后的时间作图。尽管缺乏早期时间点的血清浓度,但所得曲线符合二室模型,表明血清消除半衰期为37小时。合成卡西酮引起的持久精神病症状似乎与其毒代动力学特征相关,如半衰期较长。最后,解释合成卡西酮的毒代动力学可能为法医学和临床目的的新型精神活性物质毒理学评估提供有用信息。