Brown Jeffrey M, Yamamoto Bryan K
Department of Pharmacology and Experimental Therapeutics, L-613, School of Medicine, Boston University, 715 Albany Street, Boston, MA 02118, USA.
Pharmacol Ther. 2003 Jul;99(1):45-53. doi: 10.1016/s0163-7258(03)00052-4.
Amphetamine-like psychostimulants are associated with long-term decreases in markers for monoaminergic neurons, suggesting neuronal loss and/or damage within the brain. This long-term "toxicity" results from formation of free radicals, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS), although the mechanism(s) of ROS and RNS formation are unclear. Mitochondria are a major source of ROS and mitochondrial dysfunction has been linked to some neurodegenerative disorders. Amphetamines also inhibit mitochondrial function, although the mechanism involved in the inhibition is uncertain. This review coordinates findings on the multiple pathways for ROS and RNS and describes a hypothesis involving mitochondrial inhibition in the initiation of amphetamine-induced cellular necrosis.
苯丙胺类精神兴奋剂与单胺能神经元标志物的长期减少有关，提示大脑内存在神经元丢失和/或损伤。这种长期的“毒性”是由自由基的形成导致的，尤其是活性氧（ROS）和活性氮（RNS），尽管ROS和RNS形成的机制尚不清楚。线粒体是ROS的主要来源，线粒体功能障碍与一些神经退行性疾病有关。苯丙胺类药物也会抑制线粒体功能，但其抑制机制尚不确定。本综述整合了关于ROS和RNS多种生成途径的研究结果，并描述了一种假说，该假说认为线粒体抑制在苯丙胺诱导的细胞坏死起始过程中起作用。
