Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA.
Curr Neuropharmacol. 2011 Mar;9(1):54-7. doi: 10.2174/157015911795016930.
Methamphetamine (METH) is a widely abused substance world over. Currently, there is no effective pharmacotherapy to treat its effects. This necessitates identification of potential novel therapeutic targets. METH interacts with sigma (σ) receptors at physiologically relevant micromolar concentrations. In addition, σ receptors are present in organs like the brain, heart, and lungs at which METH acts. Additionally, σ receptors have been implicated in various acute and subchronic effects like locomotor stimulation, development of sensitization and neurotoxicity, where σ receptor antagonists attenuate these effects. σ Receptors may also have a role in METH-induced psychiatric complications such as depression, psychosis, cognitive and motor deficits. The neurotoxic effects of METH, which are cause for concern, can be prevented by σ receptor antagonists in mice. Mechanistically, METH-induced neurotoxicity involves factors like dopamine release, oxidative stress, endoplasmic reticulum stress, activation of mitochondrial death cascades, glutamate release, apoptosis, microglial activation, and hyperthermia. This review compiles studies from the literature that suggests an important role for σ receptors in many of the mechanisms of METH-induced neurotoxicity.
甲基苯丙胺（METH）是一种在世界范围内广泛滥用的物质。目前，尚无有效的药物疗法来治疗其影响。这就需要确定潜在的新治疗靶点。METH 在生理相关的微摩尔浓度下与西格玛（σ）受体相互作用。此外，σ 受体存在于大脑、心脏和肺部等器官中，METH 在这些器官中发挥作用。此外，σ 受体还与各种急性和亚慢性作用有关，如运动刺激、敏化和神经毒性的发展，其中 σ 受体拮抗剂可减轻这些作用。σ 受体也可能在 METH 引起的精神并发症中发挥作用，如抑郁、精神病、认知和运动缺陷。在小鼠中，σ 受体拮抗剂可以预防 METH 引起的神经毒性，这令人担忧。从机制上讲，METH 诱导的神经毒性涉及多巴胺释放、氧化应激、内质网应激、线粒体死亡级联的激活、谷氨酸释放、细胞凋亡、小胶质细胞激活和体温升高。这篇综述汇集了文献中的研究，表明 σ 受体在 METH 诱导的神经毒性的许多机制中起重要作用。
