Distribution of neutral prilocaine in a phospholipid bilayer: Insights from molecular dynamics simulations

Abstract

AbstractIn this work, we report a 20‐ns constant pressure molecular dynamics simulation of prilocaine (PLC), an amine–amide local anesthetic, in a hydrated liquid crystal bilayer of 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphatidylcholine. The partition of PLC induces the lateral expansion of the bilayer and a concomitant contraction in its thickness. PLC molecules are preferentially found in the hydrophobic acyl chains region, with a maximum probability at ∼12 Å from the center of the bilayer (between the C(4) and C(5) methylene groups). A decrease in the acyl chain segmental order parameter, |SCD|, compared to neat bilayers, is found, in good agreement with experimental 2H‐NMR studies. The decrease in |SCD| induced by PLC is attributed to a larger accessible volume per lipid in the acyl chain region. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008