Abstract
Local anesthetics are known to be typical drugs which act directly on biomembranes. However, the molecular mechanism of anesthetic action is still uncertain. In order to clarity the action mechanism, the partition coefficient of anesthetics to lipid membranes is necessarily important. Most local anesthetics in clinical use are tertiary amine compounds that exist in neutral and/or positively charged species, depending on the pH of the solution. In this study, we prepared coated wire electrodes sensitive to the local anesthetic dibucaine cation, and determined the partition coefficient of anesthetics into a lipid membrane. Moreover, we focused our attention on the pH-dependence of the partition coefficient in order to elucidate the contribution of charged- and uncharged-dibucaine to the lecithin membrane/buffer partition coefficients. The lecithin membrane/buffer partition coefficient was directly determined by the dibucaine cation sensor as a function of the anesthetic concentration and the pH. The limiting partition coefficient extrapolated to infinite dilution was employed because the values of partition coefficients were dependent upon the dibucaine concentration. The limiting partition coefficient increased with an increase in the pH. This means that uncharged species increased with an increase in the pH because pKa of dibucaine is 8.72 at 25°C. The partition coefficients of charged and uncharged dibucaine into the lecithin membranes were estimated from the pH-dependence of the limiting partition coefficients. The partition coefficients were 1.6×104 and 8.6×106 for charged and uncharged dibucaine, respectively. The electrodes were applied satisfactorily for determining for the partition coefficient of local anesthetic dibucaine into biomembranes.
