中国药物警戒 ›› 2024, Vol. 21 ›› Issue (4): 391-396.
DOI: 10.19803/j.1672-8629.20230326

• 基础与临床研究 • 上一篇    下一篇

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

王静文, 徐代月, 陈华#, 尹利辉*   

  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
  • 收稿日期:2023-05-26 出版日期:2024-04-15 发布日期:2024-04-18
  • 通讯作者: *尹利辉,男,硕士,主任药师,药物质量控制与检测分析。E-mail: yinlihui@nifdc.org.cn,#为共同通信作者。
  • 作者简介:王静文,女,硕士,助理研究员,药物质量控制与检测分析。
  • 基金资助:
    国家重点研发计划（2021YFF0600804）

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

WANG Jingwen, XU Daiyue, CHEN Hua#, YIN Lihui*   

  1. 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
  • Received:2023-05-26 Online:2024-04-15 Published:2024-04-18

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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、0.37 μmol·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）%,IC50为19.482 μmol·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）%,IC50>30 μmol·L-1（n=15）。阳性对照药品多菲莱德0.001 85、0.005 56、0.016 67、0.050 00、0.150 00μmol·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）%、IC50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。

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

Abstract: Objective To compare the effect of ropivacaine hydrochloride and (R)- ropivacaine hydrochloride on the human-ether-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 30.00 μmol·L-1. The half-maximal inhibitory concentration (IC50) of ropivacaine hydrochloride on hERG was 19.482 μmol·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 0.37 μmol·L-1. The half-maximal inhibitory concentration (IC50) of (R)-ropivacaine hydrochloride on hERG exceeded 30 μmol·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 0.001 85, 0.005 56, 0.016 67, 0.050 00 and 0.150 00 μmol·L-1. The half-maximal inhibitory concentration (IC50) of dofetilide on hERG was 0.015 μmol·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.

Key words: ropivacaine hydrochloride, (R)-ropivacaine hydrochloride, amide local anesthetic, manual patch clamp method, HEK 293 cells, hERG potassium channel, stereoselectivity

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