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Rate-dependent blockade of a potassium current in human atrium by the antihistamine loratadine

机译:抗组胺氯雷他定对人心房钾电流的速率依赖性阻断

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摘要

The antihistamine loratadine is widely prescribed for the treatment of symptoms associated with allergies. Although generally believed to be free of adverse cardiac effects, there are a number of recent reports suggesting that loratadine use may be associated with arrhythmias, in particular atrial arrhythmias.Nothing is known regarding the potassium channel blocking properties of loratadine in human cardiac cells. Using the whole-cell patch clamp technique, the effects of loratadine on the transient outward K current (Ito), sustained current (Isus), and current measured at −100 mV (IK1 and Ins), the major inward and outward potassium currents present in human atrial myocytes, were examined in order to provide a possible molecular mechanism for the observed atrial arrhythmias reported with loratadine use.Loratadine rate-dependently inhibited Ito at therapeutic concentrations with 10 nM loratadine reducing Ito amplitude at a pacing rate of 2 Hz by 34.9±6.0%. In contrast, loratadine had no effect on either Isus or current measured at −100 mV.These results may provide a possible mechanism for the incidences of supraventricular arrhythmias reported with the use of loratadine.
机译:抗组胺氯雷他定广泛用于治疗与过敏有关的症状。尽管通常认为没有氯胺定对心脏有不良影响,但最近有许多报道表明氯雷他定的使用可能与心律不齐有关,尤其是房性心律失常。关于氯雷他定在人心脏细胞中的钾通道阻滞特性尚无定论。使用全细胞膜片钳技术,氯雷他定对瞬态外向K电流(Ito),持续电流(Isus)和在−100 mV下测量的电流(IK1和Ins)的影响,主要存在向内和向外的钾电流对人心房肌细胞中的氯雷他定进行了研究,以便为观察到的氯雷他定使用引起的房性心律失常提供可能的分子机制。氯雷他定在治疗浓度下以10 nM氯雷他定速率依赖性地抑制Ito,以2 Hz的起搏率将Ito振幅降低34.9。 ±6.0%。相比之下,氯雷他定对Isus或在-100 mV下测得的电流均无影响,这些结果可能为氯雷他定报道的室上性心律失常的发生提供了可能的机制。

著录项

  • 作者

    Crumb, William J;

  • 作者单位
  • 年度 1999
  • 总页数
  • 原文格式 PDF
  • 正文语种 en
  • 中图分类
  • 入库时间 2022-08-20 20:37:44

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