河鲀毒素——一种具有缓解癌性疼痛潜力的药物  

Tetrodotoxin——a Promising Drug to Relieve Cancer Pain

作　　者：张梦倩 储智勇 钱晓明 王梓涵 刘德祥 龙程[1,2] ZHANG Meng-Qian;CHU Zhi-Yong;QIAN Xiao-Ming;WANG Zi-Han;LIU De-Xiang;LONG Cheng(Guangzhou Panyu Central Hospital,South China Normal University-Panyu Central Hospital Joint Laboratory of Basic and Translational Medical Research,Guangzhou 511400,China;School of Life Sciences,South China Normal University,Guangzhou 510631,China;Zhongyang Biotechnology(Shanghai)Co.Ltd,Shanghai 200002,China;School of Life Sciences,Xuzhou Medical University,Xuzhou 221004,China)

机构地区：[1]广州市番禺区中心医院,华南师范大学-番禺区中心医院基础与转化医学联合实验室,广州511400 [2]华南师范大学生命科学学院,广州510631 [3]中洋生物科技(上海)股份有限公司,上海200002 [4]徐州医科大学生命科学学院,徐州221004

出　　处：《生物化学与生物物理进展》2023年第7期1584-1596,共13页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(31871170);广东省自然科学基金(2021A1515010804,2023A1515010899)资助项目。

摘　　要：河鲀毒素(tetrodotoxin,TTX)是一种剧毒的生物碱类天然神经毒素,具有选择性阻断钠离子通道作用。人体摄入TTX后会产生致命影响,对人类的致死剂量范围1.5~2.0 mg(血药浓度9μg/L)。但以远低于其半数致死量(LD50)给患者施用TTX时,却可以治疗多种疾病,包括海洛因和可卡因戒断症状、脊髓损伤、脑外伤、肿瘤、神经性疼痛和内脏疼痛等。研究人员经过几十年不懈地探索,在TTX应用于生物医学领域,尤其是治疗癌症相关疼痛方面取得可喜进展,本文着重介绍TTX作为缓解癌性疼痛药物的临床开发、作用的有效性和安全性等最新结果,展示TTX缓解癌性疼痛的前景。Tetrodotoxin(TTX)is a highly toxic alkaloid natural neurotoxin that selectively blocks sodium ion channels.As a poison,TTX has lethal effects when ingested in humans,with lethal doses ranging from 1.5 mg to 2.0 mg(9μg/L in plasma).However,when TTX is administered to patients at levels well below its median lethal dose(LD50),it can treat a variety of medical diseases,including heroin and cocaine withdrawal symptoms,spinal cord injury,traumatic brain injury,tumor,neuropathic pain,and visceral pain.Cancer pain is generally treated with opioids,but it has certain dependence and addiction.After decades of unremitting exploration,researchers have made gratifying progress in the application of TTX in the field of biomedicine,especially in the treatment of cancer-related pain.Here we first review voltage-gated sodium channels(VGSCs),which are transmembrane proteins composed of a largeαsubunit and one or moreβsubunits.VGSCs play an important role in pain and are typically classified as TTX-sensitive or TTX-resistant channels.Furthermore,we focus on roles of three VGSC subtypes Nav1.7,Nav1.8 and Nav1.9,and present the current status of research progress in the field of cancerrelated pain.We also discuss the binding sites,tolerability,delivery and supply of TTX.Finally,we summarize the most relevant recent advances in the clinical development,efficacy and safety of TTX as a drug for relieving cancer pain,showing the promise of TTX in cancer pain relief.On this basis,the limitations of existing research are pointed out,and the research directions of TTX in relieving cancer pain and the development of targeted analgesic drugs in the future are prospected.

关 键 词：河鲀毒素 电压门控钠通道 癌性疼痛 

分 类 号：Q4[生物学—生理学] Q5