长时间暴露于雷梅西维尔抑制了人类以太-A-Go-Go相关基因电流
Enoch Amarh1, James E Tisdale1,2, Brian R Overholser1,2
1Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN; and.
用于COVID-19治疗的雷梅西维尔可以通过改变hERG电流来影响心律,特别是在长时间暴露的情况下. 需要进一步的研究,以了解它的潜力延长QTc间隔并引起Torsade de pointes.
科学领域:
- 心血管药理学心血管药理学
- 分子心脏病学分子心脏病学
- 药物安全评估 药物安全评估
背景情况:
- 雷姆迪西维尔 (Remdesivir,简称RDV) 是一种已被批准用于COVID-19治疗的抗病毒药物.
- 病例报告表明,RDV可能会延长QTc间隔并诱导torsade de pointes.
- 关于RDV对人类以太-a-go-go相关基因 (hERG) 通道的抑制存在相互矛盾的数据.
研究的目的:
- 研究雷梅西维尔及其代谢物GS-441524对hERG电流的影响.
- 评估急性和长时间暴露对hERG通道功能的影响.
主要方法:
- 使用了人类胚胎脏293个细胞稳定地表达hERG.
- 采用全电池电压协议来测量hERG电流.
- 测试了remdesivir和GS-441524的各种度.
主要成果:
- 对雷梅西维尔和GS-441524的急性暴露没有影响hERG电流或半激活电压 (V1/2).
- 用100nM和1μM的长期治疗显著减少了峰尾电流.
- 长时间暴露于雷德西维尔药物会降低hERG电流密度.
结论:
- 长时间暴露于雷梅西维尔,但不是急性暴露,可以减少hERG电流密度.
- 雷梅西维尔延长QTc间隔并诱导torsade de pointes的潜力需要进一步调查.
- 这些发现有助于了解雷梅西维尔的心脏安全概况.
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