Interaction of four local anesthetics with phospholipid bilayer membranes: permeability effects and possible mechanisms.

Sodium 22 efflux was measured, at various temperatures, in the presence of different local anesthetics (dibucaine, tetracaine, benzocaine, procaine) in multilamellar liposomes composed of saturated phosphatidylcholines and dicetyl phosphate. These liposomes display a permeability maximum in the temperature region of their respective phase transitions. Local anesthetics cause this permeability maximum to occur at a lower temperature and also increase its magnitude. Binding of the anesthetics to these liposomes displays a biphasic temperature curve with a maximum in the vicinity of the transition temperature. In addition there appears to be a linear relationship between aqueous anesthetic concentrations causing equal permeability effects and corresponding membrane concentrations. All of the anesthetics decrease the cooperativity of the lipid phase transition and this is probably an important factor underlying induced permeability effects. However several observations suggest that additional factors are also important and we have postulated that one such factor is the preferential binding of the anesthetics to phase boundary regions.