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Updated: May 26, 2026

Realistic Membrane Modeling Using Complex Lipid Mixtures in Simulation Studies
Published on: September 1, 2023
R(+)-, Rac-, and S(-)-bupivacaine stereostructure-specifically interact with membrane lipids at cardiotoxically
Hironori Tsuchiya1, Maki Mizogami
1Department of Dental Basic Education, Asahi University School of Dentistry, Gifu, Japan. hiro@dent.asahi-u.ac.j
Abstract:
It remains questionable whether local anesthetics can interact with membrane lipids at clinically relevant concentrations to show the difference between enantiomers. We compared the effects of bupivacaine stereoisomers on biomimetic membranes containing cardiolipin and cholesterol. Bupivacaine interacted with the membranes at cardiotoxic 5 μM with the potency being S(-)-enantiomer < racemate < R(+)-enantiomer, which agreed with the rank order of their cardiotoxicity. Such differences became greater with decreasing drug concentrations, possibly explaining the inconsistent cardiotoxic potencies of bupivacaine stereoisomers reported previously. The interactivity with biomembranes may in part contribute to the mode of toxic action of local anesthetics.
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