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卡西酮邻苯二甲酰亚胺诱导的单胺能毒性:一项体外研究。

Monoaminergic toxicity induced by cathinone phthalimide: An in vitro study.

作者信息

Lantz Susan M, Rosas-Hernandez Hector, Cuevas Elvis, Robinson Bonnie, Rice Kenner C, Fantegrossi William E, Imam Syed Z, Paule Merle G, Ali Syed F

机构信息

Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Rd, HFT-132, Jefferson, AR, 72079, United States.

Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA/NIAAA 9800 Medical Center Drive Rm 228A, MSC-3373, Bethesda, MD, 20892, United States.

出版信息

Neurosci Lett. 2017 Aug 10;655:76-81. doi: 10.1016/j.neulet.2017.06.059. Epub 2017 Jul 3.

Abstract

Bath salts, or synthetic cathinones, have cocaine-like or amphetamine-like properties and induce psychoactive effects via their capacity to modulate serotonin (5-HT) and dopamine (DA). Structurally distinct synthetic cathinones are continuously being generated to skirt existing drug laws. One example of these modified compounds is cathinone phthalimide (CP), which has already appeared on the global market. The lack of toxicological studies on the effects of CP on monoaminergic systems led to the development of the present study in order to generate an acute toxicity profile for CP, and to clarify whether it primarily affects both dopamine and serotonin, like the synthetic cathinones mephedrone and methylone, or primarily affects dopamine, like 3, 4-methylenedioxypyrovalerone (MDPV). For the first time, the toxicity profile of CP (10μM-1000μM) is reported. In pheochromocytoma cells, exposure to CP induced cell death, and altered mitochondrial function, as well as intracellular DA and 5-HT levels; at the same time, reduced glutathione (GSH) levels remained unaffected. This seems to indicate that CP functions like mephedrone or methylone. The role of CP metabolites, the effect of CP induced hyperthermia on neurotoxicity, and its ability to traverse the blood-brain barrier warrant further consideration.

摘要

浴盐,即合成卡西酮,具有类似可卡因或安非他命的特性,并通过调节血清素(5-羟色胺,5-HT)和多巴胺(DA)的能力产生精神活性作用。结构各异的合成卡西酮不断涌现,以规避现行的药品法律。这些经过改良的化合物之一是卡西酮邻苯二甲酰亚胺(CP),它已出现在全球市场上。由于缺乏关于CP对单胺能系统影响的毒理学研究,因此开展了本研究,旨在生成CP的急性毒性概况,并阐明它是否像合成卡西酮甲氧麻黄酮和甲酮那样主要影响多巴胺和血清素,或者像3,4-亚甲基二氧吡咯戊酮(MDPV)那样主要影响多巴胺。首次报告了CP(10μM - 1000μM)的毒性概况。在嗜铬细胞瘤细胞中,暴露于CP会导致细胞死亡,并改变线粒体功能以及细胞内多巴胺和血清素水平;同时,还原型谷胱甘肽(GSH)水平不受影响。这似乎表明CP的作用方式与甲氧麻黄酮或甲酮类似。CP代谢物的作用、CP诱导的体温过高对神经毒性的影响及其穿越血脑屏障的能力值得进一步研究。

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