Molecular properties of local anesthetics as predictors of affinity for nicotinic acetylcholine receptors.
Molecular properties of local anesthetics as predictors of affinity for nicotinic acetylcholine receptors.
复制标题
局部麻醉剂的分子特性作为烟碱乙酰胆碱受体亲和力的预测因子。
DOI：
10.1002/jnr.21402
复制
发表时间：
2007
影响因子：
4.2
通讯作者：
Oswald,RobertE
中科院分区：
文献类型：
--
作者：
Pagan,OneR;Sivaprakasam,Kannan;Oswald,RobertE
在脊麻中，局部麻醉药(LAS)的作用不能完全用钠通道抑制来解释。其他靶点包括神经元烟碱型乙酰胆碱受体(NAChRs)。通过抑制[~3H]TCP结合的方法测量了鱼雷口径烟酸受体的LA亲和力，并与分子体积、比表面积、相对分子质量和辛醇-水分配系数的对数(P和D)相关。为了了解与nAChR相互作用的重要分子决定因素，我们分别比较了酯类和酰胺类LAS。此外，还分别考虑了与LA分子的芳香族/连接基和亲水性的关联性。酯类LAS的IC50与分子中芳香族/连接基的分子体积、比表面积、相对分子质量和logP相关性较好，而酰胺类LAS的IC50与基于亲水半分子的四个参数相关性较好。这些相关性被用来预测各种LAS的IC50(包括这里没有研究的几个)，并将这些值与公布的值进行比较。IC50的预测值与已发表的神经元和电斑脱敏的nAChR的结果很好地相关，这表明这些结果可以推广到包括神经元的nAChR。©2007 Wiley-Liss Inc.
In spinal anesthesia, the effects of local anesthetics (LAs) are not completely explained by sodium channel inhibition. Other targets include neuronal nicotinic acetylcholine receptors (nAChRs). LA affinities for theTorpedo californicanAChR were measured by inhibition of [3H]TCP binding and correlated with molecular volume, surface area, molecular weight, and log of the octanol‐water partition coefficients (P and D). To understand the molecular determinants important for interaction with the nAChR, ester and amide LAs were compared separately. Also, correlations with the aromatic/linker half and the hydrophilic half of the LA molecules were considered individually. The IC50s of the ester LAs correlated better with the molecular volume, surface area, molecular weight, and log P of the aromatic/linker half of the molecules; whereas the IC50s for amide LAs correlated better with the four parameters based on the hydrophilic half. These correlations were used to predict the IC50of various LAs (including several not studied here) and to compare these values with the published values. The predicted values of IC50correlated well with the published results both for neuronal and for electroplaque‐desensitized nAChR, suggesting that the results can be generalized to include neuronal nAChRs. © 2007 Wiley‐Liss, Inc.