溴化钠:对不同模式的癫痫样活动、细胞外pH值变化和gaba能抑制的影响。
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Meierkord H, Grunig F, Gutschmidt U, Gutierrez R, Pfeiffer M, Draguhn A, Bruckner C, Heinemann U
溴化钠:对不同模式的癫痫样活动、细胞外pH值变化和gaba能抑制的影响。
中华药物学杂志。2000年1月;361(1):25-32。
- PubMed ID
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10651143 (PubMed视图］
- 摘要
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关于溴化物抗惊厥效力的结果一直受到质疑，其作用机制尚不清楚。使用联合大鼠海马-内嗅皮层片，我们分析了NaBr对两种不同癫痫模型(低ca2 +和低mg2 +模型)中四种癫痫样放电的影响。NaBr浓度依赖性地降低了频率，并最终阻止了低Ca2+诱导的放电。低Mg2+诱导的短期复发放电也以浓度依赖的方式减少。在内嗅皮层，癫痫发作样事件的频率减少了3和5 mM, 7 mM NaBr阻断了放电。此外，对大多数临床使用的抗惊厥药物无反应的内嗅皮层的晚期复发性放电在10和15 mM的浓度下减少，在30 mM的NaBr下完全阻断。在pH敏感微电极上观察到NaBr与乙酰唑胺在对照条件下和刺激后对细胞外pH的影响不同。乙酰唑胺在1 mM时可使δ pH可逆酸化:0.2+/-0.14静止时，而在5 mM NaBr时细胞外pH没有变化。乙酰唑胺增加了CA1区辐射层重复刺激引起的短暂碱中毒，减少了随后的酸中毒。NaBr也增加了碱中毒，但对随后的酸中毒无影响。 A significant increase in paired-pulse inhibition was seen in a paired-pulse stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell patch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity which is likely to be caused by its effects on membrane excitability, by an increase in GABAergic inhibition and is less likely caused by its effects on extracellular pH.