Partitioning of local anesthetic dibucaine into bilayer membranes of dimyristoylphosphatidylcholine

Binding of a local anesthetic dibucaine to dimyristoylphosphatidylcholine (DMPC) bilayer membranes was studied by using an ion-selective electrode sensitive to dibucaine cation. DMPC bilayer membrane-buffer partition coefficient was directly determined as a function of anesthetic concentration, temperature and FH. The limiting partition coefficient extrapolated to infinite dilution was employed because the values of partition coefficients were dependent upon the dibucaine concentration. DMPC multilamellar vesicles undergo the thermotropic pretransition from the lamellar gel (L-beta') to the ripple gel (P-beta') phase as well as the main transition from the P-beta' phase to the liauid crystal (L-alpha) phase. The limiting partition coefficients at pH 5.4 were 2000, 5500 and 32000 for the L-beta', P-beta' and L-alpha, phases, respectively. Each of the three states of membranes exhibited a different receptivity to dibucaine partitioning. The limiting partition coefficients were determined as a function of pH at the temperatures corresponding to three states of membranes. The partition coefficients of charged and uncharged anesthetic dibucaine into the DMPC bilayer membranes were estimated from the pH-dependence of the limiting partition coefficients. The three states of DMPC membranes were more receptive to the uncharged dibucaine than the charged species. (C) 1997 Elsevier Science B.V.