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N-水杨酰色胺,一种新型抗惊厥药物,作用于电压依赖性钠、钙和钾离子通道。

N-salicyloyltryptamine, a new anticonvulsant drug, acts on voltage-dependent Na+, Ca2+, and K+ ion channels.

作者信息

Araújo Démetrius Antonio Machado, Mafra Roberta Amaral, Rodrigues Andréia Laura Prates, Miguel-Silva Válter, Beirão Paulo Sérgio Lacerda, de Almeida Reinaldo Nóbrega, Quintans Lucindo, de Souza Maria Fátima Vanderlei, Cruz Jader Santos

机构信息

Department of Molecular Biology, CCEN, UFPB, Brazil.

出版信息

Br J Pharmacol. 2003 Dec;140(7):1331-9. doi: 10.1038/sj.bjp.0705471.

Abstract
  1. The aim of this work was to study the effects of N-salicyloyltryptamine (STP), a novel anticonvulsant agent, on voltage-gated ion channels in GH3 cells. 2. In this study, we show that STP at 17 microM inhibited up to 59.2+/-10.4% of the Ito and 73.1+/-8.56% of the IKD K+ currents in GH3 cells. Moreover, the inhibitory activity of the drug STP on K+ currents was dose-dependent (IC50=34.6+/-8.14 microM for Ito) and partially reversible after washing off. 3. Repeated stimulation at 1 Hz (STP at 17 microM) led to the total disappearance of Ito current, and an enhancement of IKD. 4. In the cell-attached configuration, application of STP to the bath increased the open probability of large-conductance Ca2+-activated K+ channels. 5. STP at 17 microM inhibited the L-type Ca2+ current by 54.9+/-7.50% without any significant changes in the voltage dependence. 6. STP at 170 microM inhibited the TTX-sensitive Na+ current by 22.1+/-2.41%. At a lower concentration (17 microM), no effect on INa was observed. 7. The pharmacological profile described here might contribute to the neuroprotective effect exerted by this compound in experimental 'in vivo' models.
摘要
  1. 本研究的目的是探讨新型抗惊厥药N-水杨酰色胺(STP)对GH3细胞电压门控离子通道的影响。2. 在本研究中,我们发现17微摩尔的STP可抑制GH3细胞中高达59.2±10.4%的Ito电流和73.1±8.56%的IKD钾电流。此外,药物STP对钾电流的抑制活性呈剂量依赖性(Ito的IC50 = 34.6±8.14微摩尔),洗脱后部分可逆。3. 以1赫兹重复刺激(17微摩尔的STP)导致Ito电流完全消失,并增强IKD电流。4. 在细胞贴附模式下,将STP应用于浴液中可增加大电导钙激活钾通道的开放概率。5. 17微摩尔的STP可抑制L型钙电流54.9±7.50%,而电压依赖性无任何显著变化。6. 170微摩尔的STP可抑制TTX敏感的钠电流22.1±2.41%。在较低浓度(17微摩尔)下,未观察到对INa的影响。7. 此处描述的药理学特征可能有助于该化合物在实验性“体内”模型中发挥神经保护作用。

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