Sigma受体拮抗剂在治疗成瘾性药物滥用致神经毒性中的研究进展

Research progress of Sigma receptor antagoinsts in the drug abuse-mediated neurotoxicity

成瘾性药物滥用是全球普遍存在的社会问题,已成为许多国家仅次于心脑血管疾病和恶性肿瘤的第3位致死病因,在我国形势也日趋严峻。脑内奖赏系统单胺学说是早期认识成瘾性药物滥用的里程碑理论,但这一学说无法解释成瘾性药物滥用者脑内由不同细胞间相互作用而引起的神经炎性级联反应最终导致的神经毒性。如何遏制成瘾性药物滥用过程中的神经炎性反应,降低神经毒性反应,是亟待解决的课题。目前,国外有关这方面的研究还处于起步阶段,仅限于大量临床病例报道;国内研究尚属空白,其确切的分子机制值得深入挖掘。本文主要针对Sigma受体拮抗剂在治疗成瘾性药物滥用导致的神经毒性中的研究进行综述,为成瘾性药物滥用致神经毒性作用提供新的药物靶标和新的治疗策略。

Drug abuse represents a serious health issue worldwide resulting personal suffering, as well as social and economic burden. Drug abuse is considered the third killer in some western societies since it affects more and more people, compared with cerebral-cardiovascular disease or malignant cancer. China faces emerging epidemics of drug abuse as evidenced that drug abusers are on the rise in recent years. Despite the recognized impact of drug abuse on the brain reward system, mechanisms underlying the ability of drug abuse to initiate a cascade of neuroinflammatory response, which finally result in widespread neurotoxicity within the complex network of cell-to-cell interactions, have not yet been fully identified. Understanding the detailed mechanisms underlying neuropathological progression induced by drug abuse is thus the next logical step that is of paramount importance. The control and eradication of neurological complications associated with drug abuse continues to be an important goal toward improving the well-being of drug abusers. This review summarizes the potential role of Sigma receptor antagoinsts in drug abuse-mediated neuroinflammation and neurotoxicity, both of which comprise the hallmark features of drug abusers. These findings will set a stage for providing a new generation of novel therapeutic agents for drug abuse involving neuroinflammation and neurotoxicity.