Interaction of local anesthetics with phospholipids in Langmuir monolayers.

We have used epifluorescence microscopy to study the interactions of two local anesthetics of the "caine" family (tetracaine and dibucaine), with Langmuir monolayers of the phospholipid dipalmitoylphosphatidylcholine (DPPC). These results show that incorporation of either dibucaine or tetracaine causes significant changes in the domain shapes of the liquid condensed phase in monolayers. In particular, at low pH, where the charged cationic form of the local anesthetics predominates, local anesthetic: DPPC monolayers formed significantly less compact liquid condensed domains with highly ramified shapes, compared to DPPC-only controls. For high pH values at which both local anesthetics are electrically neutral, the liquid condensed domains in mixed monolayers resembled that of DPPC-only controls, indicating that these effects have their origins in electrostatic interactions between the local anesthetics and the phospholipid headgroups. Epifluorescence images obtained using the intrinsic fluorescence of dibucaine indicated that dibucaine partitions into both the liquid condensed and liquid expanded phases.