封锁的HERG人类心脏K(+)通道的抗抑郁药物阿米替林。

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乔SH, Youm JB,李有限公司Earm你们工作

封锁的HERG人类心脏K(+)通道的抗抑郁药物阿米替林。

Br J杂志。2000年4月,129 (7):1474 - 80。doi: 10.1038 / sj.bjp.0703222。

PubMed ID

10742304 (在PubMed

]

文摘

1。阿米替林已经知道引起QT延长和带条de同构导致突然死亡。我们研究阿米替林的影响在人类ether-a-go-go-related基因(HERG)频道表达非洲爪蟾蜍卵母细胞,迅速激活延迟整流K(+)电流(I (Kr))在大鼠心房细胞。2。稳态电流的振幅和尾电流HERG都减少了阿米替林剂量依赖性。减少更加明显在更积极的潜力,这表明块HERG阿米替林是电压依赖性。IC(50)阿米替林块HERG电流逐渐减少根据去极化:集成电路(50)值在-30年,-10年,30 + 10 + mV分别为23.0,8.71,5.96和4.66 microM,分别。3所示。块HERG阿米替林是使用依赖:展示一个快得多块激活频率更高。后续频率高后激活频率减少,导致部分缓解HERG封锁。 4. Steady-state block by amitriptyline was obtained while depolarization to +20 mV for 0.5 s was applied at 0.5 Hz: IC(50) was 3.26 microM in 2 mM [K(+)](o). It was increased to 4. 78 microM in 4 mM [K(+)](o), suggesting that the affinity of amitriptyline on HERG was decreased by external K(+). 5. In rat atrial myocytes bathed in 35 degrees C, 5 microM amitriptyline blocked I(Kr) by 55%. However, transient outward K(+) current (I(to)) was not significantly affected. 6. In summary, the data suggest that the block of HERG currents may contribute to arrhythmogenic side effects of amitriptyline.

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药物靶点

药物	目标	类	生物	药理作用	行动
阿米替林	HERG人类心脏K +通道(蛋白质组)	蛋白质组	人类	未知的	拦截器	细节