镇痛药潜在依赖性及其非临床安全性评价研究进展  

Research progress on potential dependence and non-clinical safety evaluation of analgesic

作　　者：李龙飞 黄芝瑛[2] 张颖丽[1] 王三龙[1] 李芊芊[1] LI Longfei;HUANG Zhiying;ZHANG Yingli;WANG Sanlong;LI Qianqian(Beijing Key Laboratory of Non-Clinical Drug Research,National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100171,China;School of Pharmaceutical Sciences,Sun Yat-Sen University,Guangzhou 510006,China)

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心、药物非临床研究北京市重点实验室,北京100171 [2]中山大学药学院,广东广州510006

出　　处：《药物评价研究》2023年第12期2717-2723,共7页Drug Evaluation Research

摘　　要：镇痛药是一类主要作用于中枢神经系统(CNS),能选择性地缓解或消除疼痛及伴随的不愉快情绪(如恐惧、紧张、焦虑等)的药物。由于镇痛药的CNS活性和对μ阿片受体的作用,存在依赖性潜在风险,已成为全球性公共卫生领域的重要问题。作为多成因的疾病,遗传学因素、神经系统因素、表观遗传因素、性别因素和环境差异都可能是镇痛药诱导依赖性潜能的作用机制;可采用多种动物行为学模型,如自身给药模型、药物辨别模型评价等,对镇痛药进行非临床依赖性评价研究。重点综述传统及新型镇痛药物依赖性的神经生物学、遗传学和表观遗传学方面的机制研究,概述非临床评价其依赖潜在性的研究方法,以期为镇痛药的安全性评价及临床用药提供参考依据。Analgesics are a class of drugs that primarily act on the central nervous system(CNS)and selectively alleviate or eliminate pain and associated unpleasant emotions such as fear,tension,and anxiety.Due to the CNS activity and effect onμopioid receptor,it's likely to pose a potential risk of dependence,has become an important problem in the field of global public health.As a multifactorial disease,genetic factors,neurological factors,epigenetic factors,gender factors,and environmental influence may all be the mechanisms of analgesic induced dependence potential;various animal behavioral models,such as self-administration models and drug discrimination model evaluations,can be used to conduct non-clinical dependence evaluation studies on analgesics.Above all,this article will focus on reviewing the mechanisms of potential dependence of traditional and new analgesics in neurobiology,genetics,and epigenetics.It will also outline the research methods for non-clinical evaluation of their dependence potential,in order to provide reference for the safety evaluation and clinical use of analgesics.

关 键 词：镇痛药 Μ阿片受体 安全性评价 药物依赖性 非临床评价 

分 类 号：R969.6[医药卫生—药理学]