Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole
Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole
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DOI：
10.1016/0014-5793(96)00355-9
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发表时间：
1996-04-29
期刊：
影响因子：
3.5
通讯作者：
Busch, AE
中科院分区：
文献类型：
--
作者：
Suessbrich, H;Waldegger, S;Busch, AE
广泛使用的组胺受体拮抗剂特非那定和阿司咪唑在用药过量或不适当的合并用药情况下显示出延长心电图记录的QT间期，表明可能与心脏K+通道相互作用。在这里，特非那定和阿司咪唑在纳摩尔浓度下都以使用和电压依赖性方式抑制非洲爪蟾卵母细胞中表达的人类ether-a-go-go相关基因（HERG）编码通道。相反，其他延迟整流（Kv1.1和I-sK）或内向整流钾通道（IRK 1）的抑制要弱得多，仅发生在高微摩尔浓度。这些结果表明，特非那定和阿司咪唑对HERG通道的阻断可能导致这些化合物的心脏副作用。
The widely used histamine receptor antagonists terfenadine and astemizole were shown to prolong the QT interval in electrocardiographic recordings in cases of overdose or inappropriate co-medications, indicating a possible interaction with cardiac K+ channels. Here, terfenadine and astemizole both inhibited the human ether-a-go-go related gene (HERG) encoded channels expressed in Xenopus oocytes at nanomolar concentrations in a use- and voltage-dependent fashion. In contrast, inhibition of other delayed rectifier (Kv1.1 and I-sK) or inward rectifier K+ channels (IRK1) was much, weaker and occurred only at high micromolar concentrations. These results suggest that blockade of HERG channels by terfenadine and astemizole might contribute to the cardiac side effects of these compounds.