手动膜片钳检测盐酸罗哌卡因及其右旋异构体对HEK293细胞hERG电流的影响  

Effect of ropivacaine hydrochloride and its dextroisomer(R)-ropivacaine hydrochloride on hERG currents using manual patch clamp method in HEK293 cells that stably overexpress hERG channel

作　　者：王静文 徐代月 陈华 尹利辉 WANG Jingwen;XU Daiyue;CHEN Hua;YIN Lihui(National Medical Products Administration Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Institute for Chemical Drug Control,National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院化学药品检定所,国家食品药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《中国药物警戒》2024年第4期391-396,共6页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2021YFF0600804)。

摘　　要：目的研究比较盐酸罗哌卡因和盐酸罗哌卡因右旋异构体对高表达hERG钾通道的HEK293细胞hERG电流的影响。方法用手动膜片钳检测转染后hERG钾通道稳定表达的HEK293细胞电流,多菲莱德做阳性药,将盐酸罗哌卡因和盐酸罗哌卡因右旋异构体依次稀释成30.00、10.00、3.33、1.11、0.37μmol·L^(-1),依次作用于细胞,记录电流变化,计算抑制率。结果盐酸罗哌卡因0.37、1.11、3.33、10、30μmol·L^(-1)对电流Iherg-tail的抑制率分别为(6.12±0.30)%、(13.04±1.20)%、(19.21±0.33)%、(35.56±0.66)%、(65.37±4.17)%,IC_(50)为19.482μmol·L^(-1)(n=15)。盐酸罗哌卡因右旋异构体0.37、1.11、3.33、10.00、30.00μmol·L^(-1)对电流Iherg-tail的抑制率分别为(4.13±3.43)%、(7.34±5.60)%、(9.49±2.75)%、(16.60±0.87)%、(31.36±1.45)%,IC_(50)>30μmol·L^(-1)(n=15)。阳性对照药品多菲莱德0.00185、0.00556、0.01667、0.05000、0.15000μmol·L^(-1)对电流Iherg-tail的抑制率分别为(7.81±2.77)%、(19.67±1.88)%、(57.16±4.39)%、(89.71±3.55)%、(99.66±0.89)%、IC_(50)为0.015μmol·L^(-1)(n=15)。结论和阳性对照药品多菲莱德比较,盐酸罗哌卡因对hERG通道为弱抑制作用,盐酸罗哌卡因右旋异构体对hERG通道为无明显抑制作用。Objective To compare the effect of ropivacaine hydrochloride and(R)-ropivacaine hydrochloride on the humanether-a-go-go-related gene(hERG)current in HEK293 cells that stably overexpress hERG potassium channels.Methods Manul patch clamp techniques were employed to investigate the effects of ropivacaine hydrochloride and(R)-ropivacaine hydrochloride on Iherg-tail in the HEK293 cell line that stably overexpresses hERG potassium channels.Results The inhibition rate of ropivacaine hydrochloride on hERG was(6.12±0.30)%,(13.04±1.20)%,(19.21±0.33)%,(35.56±0.66)%and(65.37±4.17)%at the doses of 0.37,1.11,3.33,10.00 and 30.00μmol·L^(-1).The half-maximal inhibitory concentration(IC_(50))of ropivacaine hydrochloride on hERG was 19.482μmol·L^(-1)(n=15).The inhibition rate of(R)-ropivacaine hydrochloride on hERG was(4.13±3.43)%,(7.34±5.60)%,(9.49±2.75)%,(16.60±0.87)%and(31.36±1.45)%at the doses of 30.00,10.00,1.11 and 0.37μmol·L^(-1).The half-maximal inhibitory concentration(IC_(50))of(R)-ropivacaine hydrochloride on hERG exceeded 30μmol·L^(-1)(n=15).The inhibition rate of dofetilide on hERG was(7.81±2.77)%,(19.67±1.88)%,(57.16±4.39)%,(89.71±3.55)%and(99.66±0.89)%at the doses of 0.00185,0.00556,0.01667,0.05000 and 0.15000μmol·L^(-1).The half-maximal inhibitory concentration(IC_(50))of dofetilide on hERG was 0.015μmol·L^(-1)(n=15).Conclusion Compared with dofetilide,ropivacaine hydrochloride has weak inhibitory effect on the hERG channel and(R)-ropivacaine hydrochloride has no obvious inhibitory effect on the hERG channel.

关 键 词：盐酸罗哌卡因 盐酸罗哌卡因右旋异构体 酰胺类局麻药 手动膜片钳 HEK293细胞 HERG钾通道 立体选择性 

分 类 号：R971.2[医药卫生—药品]