Casati Sara, Ravelli Alessandro, Dei Cas Michele, Bergamaschi Roberta F, Vanerio Sofia, Sicuro Lea, Faraone Chiara, Rossi Marta, Galante Nicola, Mollica Luca, Roda Gabriella, Rota Paola, Battistini Alessio
Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and Dental Science, University of Milan, Via Luigi Mangiagalli, 37, Milan, 20133, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, Milan, 20135, Italy.
J Anal Toxicol. 2025 Jul 1;49(6):384-393. doi: 10.1093/jat/bkaf048.
A drug-related fatality involving 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) is here reported. Belonging to the class of synthetic cathinones (SCs), MDPHP is a 3,4-methylenedioxy-derived designer (MDDs) drug with a pyrrolidine moiety and an alkyl portion with six carbon atoms. Other MDD pyrrolidine derivatives belong to the alkyl homologous series (C3-C5) and are known as 3,4-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP), 3,4-methylenedioxy-α-pyrrolidinobutyrophenone (MDPBP) and 3,4-methylenedioxypyrovalerone (MDPV). MDDs are psychostimulant drugs of abuse that primarily act on monoamine transporters; little is known about their off-target liability. Recently, MDPHP has gained attention due to increasing seizures and involvement in human intoxications, but currently there is a lack of data about its pharmaco-toxicological effects. In the case reported here, a 58-year-old man with a history of MDPV addiction was found dead in a waterway. While no evidence of natural disease or trauma was found to account for the death, toxicological analysis revealed the presence of MDPHP in addition to MDPPP, MDPV, MDPBP, clonazepam, and citalopram. Since no standards of MDPPP and MDPBP were available at the time of the analysis, LC-QTOF analysis of the drugs and their metabolites were performed. The following concentrations of MDPHP were reported: 350 ng/mL in femoral blood (FB), 110 ng/mL in cardiac blood (CB), 1900 ng/mL in urine, 3000 ng/mL in bile, 490 ng/g in kidney, 80 ng/g in liver, 480 ng/g in lung, 98 ng/g in brain, 700 ng/mL in gastric content and 8 ng/mg in pubic hair. Other MDDs concentrations in biological fluids and tissue were significantly lower than MDPHP suggesting their presence as synthetic impurities. Finally, to better understand the binding properties of the abovementioned MDDs to several documented transporters and receptors, an in silico evaluation was performed. The medical examiner reported that the cause of death was an acute multidrug intoxication by MDPHP and clonazepam in presence of MDPPP, MDPV, MDPBP and citalopram.
本文报告了一起与3,4-亚甲基二氧基-α-吡咯烷基己酰苯（MDPHP）相关的药物致死案例。MDPHP属于合成卡西酮类（SCs），是一种具有吡咯烷部分和六个碳原子烷基部分的3,4-亚甲基二氧基衍生的设计药物（MDDs）。其他MDD吡咯烷衍生物属于烷基同系物系列（C3 - C5），被称为3,4-亚甲基二氧基-α-吡咯烷基苯丙酮（MDPPP）、3,4-亚甲基二氧基-α-吡咯烷基丁酰苯（MDPBP）和3,4-亚甲基二氧吡咯戊酮（MDPV）。MDDs是主要作用于单胺转运体的滥用精神刺激药物；关于它们的脱靶效应知之甚少。最近，由于缉获量增加以及涉及人体中毒事件，MDPHP受到了关注，但目前缺乏关于其药理毒理学效应的数据。在本报告的案例中，一名有MDPV成瘾史的58岁男性被发现死于一条水道中。虽然未发现自然疾病或外伤迹象可解释死亡原因，但毒理学分析显示除了MDPPP、MDPV、MDPBP、氯硝西泮和西酞普兰外，还存在MDPHP。由于分析时没有MDPPP和MDPBP的标准品，因此对这些药物及其代谢物进行了液相色谱 - 四极杆飞行时间质谱（LC - QTOF）分析。报告的MDPHP浓度如下：股血（FB）中为350 ng/mL，心血（CB）中为110 ng/mL，尿液中为1900 ng/mL，胆汁中为3000 ng/mL，肾脏中为490 ng/g，肝脏中为80 ng/g，肺中为480 ng/g，脑中为98 ng/g，胃内容物中为700 ng/mL，阴毛中为8 ng/mg。生物体液和组织中其他MDDs的浓度显著低于MDPHP，表明它们作为合成杂质存在。最后，为了更好地了解上述MDDs与几种已记录的转运体和受体的结合特性，进行了计算机模拟评估。法医报告称，死亡原因是在存在MDPPP、MDPV、MDPBP和西酞普兰的情况下，由MDPHP和氯硝西泮引起的急性多药中毒。
