基于μ阿片受体的双/多靶点镇痛药物研究进展  

Recent Advances in Dual/Multi-Targeted Analgesics Based on μ Opioid Receptor

作　　者：韩晓敏 殷明月 宋杰 庄涛 HAN Xiaomin;YIN Mingyue;SONG Jie;ZHUANG Tao(School of Pharmacy,Jiangsu Ocean University,Lianyungang 222000,China)

机构地区：[1]江苏海洋大学药学院,江苏连云港222000

出　　处：《中国药学杂志》2024年第22期2107-2115,共9页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(82304275);江苏省高等学校自然科学研究项目资助(23KJB350002);江苏省研究生科研与实践创新计划项目资助(KYCX2024-19,KYCX2023-44)。

摘　　要：疼痛的治疗与管理是与人类生活息息相关的全球公共卫生安全问题,各种疼痛困扰着全世界约20%的成年人。传统的阿片类镇痛药物主要通过激活μ阿片受体(μopioid receptor,MOR)而发挥镇痛效果,但其普遍存在呼吸抑制、成瘾、便秘等严重副作用,在全球范围内造成日益严重的“阿片危机”现象。因此针对无/低副作用镇痛药物的研发显得尤为重要与迫切。多靶点药物治疗策略针对疾病网络系统中的两个或多个相关靶点,可以同步调节复杂疾病网络系统中的多个环节,从而实现更优的临床疗效与安全性。在疼痛药物研究领域,鉴于MOR在疼痛信号通路中的重要作用,基于MOR的双/多靶点药物研发也已成为无/低副作用镇痛药物研究的主流策略之一。本文对近年来报道的MOR双/多靶点药物进行综述,以期为基于MOR的无/低副作用镇痛药物的研发提供参考。Pain management remains as a global public health issue,with 20%of the adult population worldwide impacted and many patients still suffer from unrelieved or undertreated pain.Classic opioids exert antinociceptive effects by activatingμopioid receptor(MOR),but they are associated with many side effects(including respiratory depression,addiction,and constipation)which have aggravated the ongoing and escalating opioid crisis in worldwide.Therefore,there is an urgent need for the development of novel analgesics free of MOR-mediated unwanted adverse effects.Multi-target therapeutics target two or more related targets in a disease network system simultaneously,which can potentially provide greater efficacy and improve treatment outcomes compared with single-target therapies.Due to the key role of MOR in regulating pain signal transmission,MOR-based multi-target ligands have been accepted as one of the mainstream strategies for designing new potent analgesics without side effects.In this review,recent advances in multitarget-directed drugs toward MOR are summarized,which may provide references for the development of potent and safer analgesics.

关 键 词：镇痛药物 Μ阿片受体 副作用 双/多靶点药物治疗 

分 类 号：R914[医药卫生—药物化学]