Catalano Alessia, Carocci Alessia, Fracchiolla Giuseppe, Franchini Carlo, Lentini Giovanni, Tortorella Vincenzo, De Luca Annamaria, De Bellis Michela, Desaphy Jean-Francois, Conte Camerino Diana
Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Bari, Italy.
Chirality. 2004 Feb;16(2):72-8. doi: 10.1002/chir.10307.
Both enantiomers of "para-hydroxymexiletine" (PHM), one of the main metabolites of mexiletine, were synthesized and fully characterized. Properties of (R)- and (S)-PHM, in terms of blocking potency and stereoselectivity on frog skeletal muscle Na(+) channels, were evaluated. The presence of a hydroxy group on the aryloxy moiety in the 4-position, as in PHM, reduced potency with respect to mexiletine in reducing I(Na max). However, PHM showed clear use-dependent behavior similar to that of mexiletine and, in contrast with what is observed with the parent compound, maintained its stereoselectivity during the use-dependent block. Chirality 16:72-78, 2004.
美西律的主要代谢产物之一“对羟基美西律”（PHM）的两种对映体均已合成并得到全面表征。评估了（R）-和（S）-PHM在阻断效力以及对青蛙骨骼肌钠通道的立体选择性方面的特性。与美西律一样，PHM的4位芳氧基部分上存在羟基，在降低最大钠电流（I(Na max)）方面相对于美西律降低了效力。然而，PHM显示出与美西律相似的明显的使用依赖性行为，并且与母体化合物所观察到的情况相反，在使用依赖性阻断过程中保持了其立体选择性。《手性》16:72 - 78，2004年。
