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首页> 外文期刊>Clinical and experimental pharmacology & physiology >In Vitro electrophysiological activity of nerispirdine, a novel 4-aminopyridine derivative.
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In Vitro electrophysiological activity of nerispirdine, a novel 4-aminopyridine derivative.

机译：nerispirdine（一种新型的4-氨基吡啶衍生物）的体外电生理活性。

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Summary 1. The non-selective K(+) channel blocker 4-aminopyridine (4-AP) has shown clinical efficacy in the treatment of neurological disorders such as multiple sclerosis. The clinical usefulness of 4-AP is hampered by its ability to produce seizures. Nerispirdine, an analogue of 4-AP, is currently under clinical investigation for the treatment of multiple sclerosis. In contrast with 4-AP, nerispirdine is not proconvulsant, suggesting mechanistic differences between the two drugs. 2. Using whole-cell patch-clamp electrophysiology, we compared the effects of 4-AP and nerispirdine on the cloned human K(+) channels K(v)1.1 and K(v)1.2, expressed in Chinese hamster ovary cells, and on voltage-dependent Na(+) channels recorded from human SH-SY5Y cells. 3. Nerispirdine inhibited K(v)1.1 and K(v)1.2 with IC(50) values of 3.6 and 3.7 micromol/L, respectively. 4-Aminopyridine was approximately 50-fold less potent at blocking these channels. Nerispirdine also inhibited voltage-dependent Na(+) channel currents recorded from human SH-SY5Y cells with an IC(50) of 11.9 micromol/L when measured from a -70 mV holding potential. In contrast, 4-AP had no effect on Na(+) channel currents. 4. The results demonstrate that nerispirdine, like 4-AP, can inhibit axonal K(+) channels and that this mechanism may underlie the ability of the drug to enhance neuronal conduction. Unlike 4-AP, nerispirdine can also inhibit neuronal Na(+) channels, a mechanism that may explain why nerispirdine lacks proconvulsant activity.
机译：总结1.非选择性K（+）通道阻滞剂4-氨基吡啶（4-AP）在治疗神经系统疾病（如多发性硬化症）中显示出临床疗效。 4-AP产生癫痫发作的能力阻碍了其临床实用性。 Nerispirdine是4-AP的类似物，目前正在临床上治疗多发性硬化症。与4-AP相比，nerispirdine并非惊厥药，提示两种药物之间存在机械差异。 2.使用全细胞膜片钳电生理学，我们比较了4-AP和那利比定对克隆的在中国仓鼠卵巢细胞中表达的人K（+）通道K（v）1.1和K（v）1.2的作用，以及人SH-SY5Y细胞记录的电压依赖性Na（+）通道上的信号。 3.奈非哌啶抑制K（v）1.1和K（v）1.2的IC（50）值分别为3.6和3.7 micromol / L。 4-氨基吡啶在阻断这些通道上的效力大约低50倍。当从-70 mV保持电势测量时，Nerispirdine还抑制人SH-SY5Y细胞记录的电压依赖性Na（+）通道电流，IC（50）为11.9 micromol / L。相反，4-AP对Na（+）通道电流没有影响。 4.结果表明，奈利哌啶像4-AP一样可以抑制轴突K（+）通道，这种机制可能是该药物增强神经元传导能力的基础。与4-AP不同的是，nerispirdine还可以抑制神经元Na（+）通道，该机制可以解释为什么nerispirdine缺乏惊厥活性。

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