Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States of America.
Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States of America.
Pharmacol Biochem Behav. 2020 Apr;191:172871. doi: 10.1016/j.pbb.2020.172871. Epub 2020 Feb 12.
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.
To determine whether the SPCs cathinone (CAT), methcathinone (MCAT), mephedrone (MMC), and methylenedioxypyrovalerone (MDPV) have lower LD50 values than MA or MDMA.
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.
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.
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.
合成致幻苯丙胺类兴奋剂（SPCs）是具有类似甲基苯丙胺（MA）和 3,4-亚甲基二氧甲基苯丙胺（MDMA）的致幻和致快感特性的药物。尽管有临床报道称人类过量使用这些药物，但仍需确定 SPCs 是否比 MA 或 MDMA 更有可能产生不良反应。
确定 SPCs 类兴奋剂卡他碱（CAT）、甲卡西酮（MCAT）、 氯胺酮（MMC）和 3,4-亚甲基二氧吡咯戊酮（MDPV）的 LD50 值是否低于 MA 或 MDMA。
雄性和雌性 C57Bl/6J 小鼠接受单次注射 6 种剂量的一种测试药物（0-160mg/kg IP）。每 20 分钟观察一次体温和行为变化，持续 2 小时，然后对幸存的小鼠进行安乐死。对器官进行称重并评估组织病理学变化。
MA 和 MDMA 的 LD50 值分别为 84.5 和 100.9mg/kg，与之前的观察结果相似。MMC 的 LD50 值为 118.8mg/kg，但其他 SPCs（CAT、MCAT、MDPV）的致死率有限，因此无法计算 LD50 值。所有药物导致的死亡均与观察到的癫痫发作有关。与高热相反，MMC、MDPV、CAT 和 MCAT 均表现出剂量依赖性的体温过低。与最初的预期相反，本研究中没有一种 SPC 的 LD50 值低于 MA 或 MDMA。
这些数据表明，在本研究条件下：（1）SPCs 的致死率低于 MA 和 MDMA；（2）SPCs 会损害体温调节；（3）SPCs 对温度的影响似乎与对致死率的影响无关。
