Interaction of local anesthetics with phospholipids in Langmuir monolayers

We have used epifluorescence microscopy to study the interactions of two lo cal anesthetics of the ''caine'' family (tetracaine and dibucaine), with La ngmuir monolayers of the phospholipid dipalmitoylphosphatidylcholine (DPPC) . These results show that incorporation of either dibucaine or tetracaine c auses significant changes in the domain shapes of the liquid condensed phas e in monolayers. In particular, at low pH, where the charged cationic form of the local anesthetics predominates, local anesthetic: DPPC monolayers fo rmed significantly less compact liquid condensed domains with highly ramifi ed shapes, compared to DPPC-only controls. For high pH values at which both local anesthetics are electrically neutral, the liquid condensed domains i n mixed monolayers resembled that of DPPC-only controls, indicating that th ese effects have their origins in electrostatic interactions between the lo cal anesthetics and the phospholipid headgroups. Epifluorescence images obt ained using the intrinsic fluorescence of dibucaine indicated that dibucain e partitions into both the liquid condensed and liquid expanded phases.