Chirality effects on the interaccions of uncharged bupivacaine with phospholipid bilayers by simulations

M. PICKHOLZ; M.F. MARTINI

Varsovia

Conferencia; 52nd International Conference on Bioscience of Lipids; 2011

ICBL

Most of local anesthetics (LA) - pain-relief drugs - posses a chiral center, that often results in a difference activities of between the drug enantiomers. For instance, this is the case of bupivacaine: both enantiomers are actives as nerve blockers. However, the R-(+) is more toxic than the S-(-) form. The racemic mixture of bupivacaine was one of the most widely used LA, due to its quality of anesthesia and prolonged duration of action, however it presents high toxicity.. Bupivacaine has a big affinity for the cellular membrane because of their amphiphatic nature (partition coefficient). In this way, a better understanding of the interaction of each enantiomer with biological membranes could provide insights, for instance, to improve their efficacy and minimize the side effects. In this work, we investigate the interaction of neutral buvipacaine (BVC) with model membranes by Molecular Dynamics (MD) simulations. We have carried out a series of simulations where both enantiomers of neutral BVC as well as the racemic mixture were taken into account. Simulations for both enantiomers show that the BVCs molecules are essentially found into the hydrophobic tail region. The BVC-R enantioner follows a bimodal distribution while the BVC-S is found, in more uniform distribution, at the bilayer center. Besides, following our previous work, we are carrying out MD simulations of these systems at the Coarse Grain level.