Chachin M, Katayama Y, Yamada M, Horio Y, Ohmura T, Kitagawa H, Uchida S, Kurachi Y
Department of Pharmacology, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim, Japan.
Eur J Pharmacol. 1999 Jun 25;374(3):457-60. doi: 10.1016/s0014-2999(99)00375-1.
Terfenadine and astemizole rarely cause cardiac arrhythmias by suppressing the cardiac rapid delayed rectifier K+ channel encoded by the human ether-a-go-go-related gene (HERG). Epinastine, however, has not been reported to have the adverse effect. We have therefore compared the effects of epinastine, terfenadine and astemizole on HERG channels expressed in Xenopus oocytes. Terfenadine and astemizole suppressed the HERG current with IC50 of 431 nM and 69 nM, respectively. In contrast, 100 microM epinastine inhibited the HERG current by only 11+/-2.1%. These results may provide an explanation for the difference in the cardiotoxicity between different nonsedating histamine H1 receptor antagonists.
特非那定和阿司咪唑通过抑制由人类醚 - 去极化相关基因（HERG）编码的心脏快速延迟整流钾通道，很少引起心律失常。然而，依匹斯汀尚未被报道有此不良反应。因此，我们比较了依匹斯汀、特非那定和阿司咪唑对非洲爪蟾卵母细胞中表达的HERG通道的影响。特非那定和阿司咪唑抑制HERG电流的IC50分别为431 nM和69 nM。相比之下，100 μM依匹斯汀仅使HERG电流抑制了11±2.1%。这些结果可能解释了不同非镇静性组胺H1受体拮抗剂在心脏毒性方面的差异。
