Interaction of "caine" type local anesthetics with phospholipids in Langmuir monolayers, (Suzanne Amador^*, Samuel D. Floyd^§, and Madison A. Compton^*) ^*Physics Department, ^§Biology Department, Haverford College, Haverford College, Haverford PA 19041.

We have used epifluorescence microscopy to study the interactions of local anesthetics of the "caine" family (tetracaine (TTC) and dibucaine (DIB)) with Langmuir monolayers of the phospholipid dipalmitoylphosphatidylcholine (DPPC). The interesting pharmacological properties of these drugs are thought to depend on their interactions with biological membranes. The results reported here show that incorporation of either DIB or TTC causes significant changes in the ordering of phospholipids in the liquid condensed (LC) phase. These changes are evidenced by the growth behavior of LC domains in monolayers containing DIB or TTC in comparison with DPPC-only controls; at low pH, the major differences were very different faceting and significantly less compact LC domain growth. Both effects indicate that the headgroup-headgroup interactions between phospholipids were strongly altered by the presence of the local anesthetics. To probe whether DIB or TTC influence the phospholipid ordering via electrostatic interactions, we obtained results for pH values well above and below the pKa of either local anesthetic. For high pH, at which both TTC and DIB are electrically neutral, the novel LC ordering observed at low pH was not present and the monolayers were almost indistinguishable from controls. Monolayers incorporating the local anesthetics were significantly more nonuniform in appearance than controls, supporting the hypothesis that the local anesthetics distribute nonuniformly throughout membranes. The distribution of dibucaine within the monolayers was detected by its intrinsic fluorescence, establishing that dibucaine partitions into both the liquid condensed and expanded phases.