Department of Pharmacology & Experimental Therapeutics, College of Pharmacology and Pharmacological Science, University of Toledo, OH, USA.
Department of Pharmacology & Experimental Therapeutics, College of Pharmacology and Pharmacological Science, University of Toledo, OH, USA; Ninevah College of Medicine, Ninevah University, Mosul, Iraq.
Pharmacol Biochem Behav. 2020 May;192:172912. doi: 10.1016/j.pbb.2020.172912. Epub 2020 Mar 19.
Methylenedioxymethamphetamine (MDMA) and methcathinone (MCAT) are abused psychostimulant drugs that produce adverse effects in human users that include hepatotoxicity and death. Recent work has suggested a connection between hepatotoxicity, elevations in plasma ammonia, and brain glutamate function for methamphetamine (METH)-induced neurotoxicity.
These experiments investigated the effect of ambient temperature on the toxicity and lethality produced by MDMA and MCAT in mice, and whether these effects might involve similar mechanisms to those described for METH neurotoxicity.
Under low (room temperature) ambient temperature conditions, MDMA induced hepatotoxicity, elevated plasma ammonia levels, and induced lethality. Under the same conditions, even a very high dose of MCAT produced limited toxic or lethal effects. High ambient temperature conditions potentiated the toxic and lethal effects of both MDMA and MCAT.
These studies suggest that hepatotoxicity, plasma ammonia, and brain glutamate function are involved in MDMA-induced lethality, as has been shown for METH neurotoxicity. The toxicity and lethality of both MDMA and MCAT were potentiated by high ambient temperatures. Although an initial mouse study reported that several cathinones were much less toxic than METH or MDMA, the present results suggest that it will be essential to assess the potential dangers posed by these drugs under high ambient temperatures.
3,4-亚甲基二氧甲基苯丙胺（MDMA）和甲卡西酮（MCAT）是被滥用的苯丙胺类兴奋剂，会对人类使用者产生肝毒性和死亡等不良反应。最近的研究表明，对于甲基苯丙胺（METH）引起的神经毒性，肝毒性、血浆氨升高和大脑谷氨酸功能之间存在联系。
这些实验研究了环境温度对 MDMA 和 MCAT 在小鼠中产生的毒性和致死作用的影响，以及这些影响是否可能涉及与 METH 神经毒性描述相似的机制。
在较低（室温）环境温度条件下，MDMA 可诱导肝毒性、血浆氨水平升高并导致死亡。在相同条件下，即使是非常高剂量的 MCAT 也只产生有限的毒性或致死作用。较高的环境温度条件增强了 MDMA 和 MCAT 的毒性和致死作用。
这些研究表明，肝毒性、血浆氨和大脑谷氨酸功能参与了 MDMA 诱导的致死作用，就像 METH 神经毒性一样。高环境温度增强了 MDMA 和 MCAT 的毒性和致死作用。尽管一项初步的小鼠研究报告称，几种卡西酮的毒性远低于 METH 或 MDMA，但目前的结果表明，在高温环境下评估这些药物的潜在危险至关重要。
