Hahin R, Kondratiev A
Department of Biological Sciences, Northern Illinois University, DeKalb 60115, USA.
J Membr Biol. 2001 Mar 15;180(2):137-45. doi: 10.1007/s002320010065.
A series of n-alkanols and phenyl-substituted n-alkanols (phi-alkanols) of increasing chain length and phenol were characterized for their ability to block action potentials (APs) in frog sciatic nerves. APs were recorded using the single sucrose-gap method. The degree of AP attenuation when the nerve was exposed to different concentrations of an alcohol was used to construct dose-response curves. The reciprocals of the half-blocking doses (ED50s) were used to obtain a measure of the potency of the alcohols. For n-alkanols and phi-alkanols, increasing the chain length by the addition of a methylene group increased the potency on average by 3.1 for both groups of alkanols. The addition of a phenyl group caused a potency increase that ranged between the values of 77 and 122. The ED50 for both groups of alkanols could not be solely predicted by the log octanol-water partition coefficient (Kow). Using linear solvation energy relations (LSER), the log ED50 could be described as a linear combination of the intrinsic (van der Waals) molar volume (VI), polarity (P), and hydrogen bond acceptor basicity (beta) and donor acidity (alpha). Size alone could not predict the ED50 for both n-alkanols and phi-alkanols. The results are consistent with the hypothesis that alkanols bind to and interact with Na channels to cause AP block. Phenyl group addition to an alkanol markedly increases the molecule's potency.
研究了一系列链长递增的正构烷醇和苯基取代正构烷醇（苯基烷醇）以及苯酚对青蛙坐骨神经动作电位（AP）的阻断能力。采用单蔗糖间隙法记录动作电位。当神经暴露于不同浓度的醇时，根据动作电位衰减程度构建剂量反应曲线。用半阻断剂量（ED50）的倒数来衡量醇的效力。对于正构烷醇和苯基烷醇，通过添加亚甲基增加链长，两组烷醇的效力平均增加3.1。添加苯基导致效力增加，增幅在77至122之间。两组烷醇的ED50不能仅通过正辛醇-水分配系数（Kow）来预测。利用线性溶剂化能关系（LSER），log ED50可以描述为固有（范德华）摩尔体积（VI）、极性（P）、氢键受体碱性（β）和供体酸度（α）的线性组合。仅分子大小不能预测正构烷醇和苯基烷醇的ED50。结果与烷醇与钠通道结合并相互作用导致动作电位阻断的假说一致。向烷醇中添加苯基可显著提高分子的效力。
