Rationale

Synthetic psychoactive cathinones (SPCs) are drugs with psychostimulant and entactogenic properties like methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). Despite clinical reports of human overdose, it remains to be determined if SPCs have greater propensity for adverse effects than MA or MDMA.

Objectives

To determine whether the SPCs cathinone (CAT), methcathinone (MCAT), mephedrone (MMC), and methylenedioxypyrovalerone (MDPV) have lower LD50 values than MA or MDMA.

Methods

Male and female C57Bl/6J mice received single injections of one of 6 doses of a test drug (0–160 mg/kg IP). Temperature and behavioral observations were taken every 20 min for 2 h followed by euthanasia of surviving mice. Organs were weighed and evaluated for histopathological changes.

Results

LD50 values for MA and MDMA, 84.5 and 100.9 mg/kg respectively, were similar to previous observations. The LD50 for MMC was 118.8 mg/kg, but limited lethality was observed for other SPCs (CAT, MCAT, MDPV), so LD50 values could not be calculated. For all drugs, death was associated with seizure, when it was observed. Rather than hyperthermia, dose-dependent hypothermia was observed for MMC, MDPV, CAT, and MCAT. Contrary to initial expectations, none of the SPCs studied here had LD50 values lower than MA or MDMA.

Conclusions

These data indicate that, under the conditions studied here: (1) SPCs exhibit less lethality than MA and MDMA; (2) SPCs impair thermoregulation; (3) effects of SPCs on temperature appear to be independent of effects on lethality.

中文翻译：

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合成的精神活性卡西酮：与甲基苯丙胺和亚甲二氧基甲基苯丙胺相比，体温过低，致死率降低。

基本原理

合成的精神活性卡西酮（SPC）是具有精神刺激和促触觉特性的药物，如甲基苯丙胺（MA）和3,4-亚甲二氧基甲基苯丙胺（MDMA）。尽管有关于人用药过量的临床报道，但仍有待确定SPC是否比MA或MDMA有更大的不良反应倾向。

目标

要确定SPC卡西酮（CAT），甲卡西酮（MCAT），甲氧麻黄酮（MMC）和亚甲二氧基吡咯烷酮（MDPV）是否具有比MA或MDMA更低的LD50值。

方法

雄性和雌性C57Bl / 6J小鼠单次注射6剂受试药物之一（0–160 mg / kg IP）。每20分钟进行一次温度和行为观察，持续2 h，然后对存活的小鼠实施安乐死。称重器官并评估组织病理学变化。

结果

MA和MDMA的LD50值分别为84.5和100.9 mg / kg，与以前的观察结果相似。MMC的LD50为118.8 mg / kg，但其他SPC（CAT，MCAT，MDPV）的致死性有限，因此无法计算LD50值。对于所有药物，观察到死亡均与癫痫发作有关。MMC，MDPV，CAT和MCAT观察到剂量依赖性的体温过低，而不是体温过高。与最初的期望相反，此处研究的所有SPC的LD50值都不低于MA或MDMA。

结论

这些数据表明，在此处研究的条件下：（1）SPC的致死性低于MA和MDMA；（2）SPC损害温度调节；（3）SPC对温度的影响似乎与对致死性的影响无关。