Preferential location of prilocaine and etidocaine in phospholipid bilayers: A molecular dynamics study

Abstract

In this work, we report a 20-ns constant pressure molecular dynamics simulation of the uncharged form of two amino–amide local anesthetics (LA), etidocaine and prilocaine, present at 1:3 LA:lipid, molar ratio inside the membrane, in the hydrated liquid crystal bilayer phase of 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphatidylcholine (POPC). Both LAs induced lateral expansion and a concomitant contraction in the bilayer thickness. A decrease in the acyl chain segment order parameter, − S CD, compared to neat bilayers, was also observed. Besides, both LA molecules got preferentially located in the hydrophobic acyl chains region, with a maximum probability at ∼12 and ∼10 Å from the center of the bilayer for prilocaine and etidocaine, respectively.