Differences in the local anaesthesia effect by lidocaine and bupivacaine based on free energy analysis

ABSTRACT

Lidocaine and bupivacaine are local anaesthetics used clinically to numb tissue in a specific area. The anaesthetic effect of lidocaine starts twice as fast as bupivacaine, although it lasts half as long or less. It is still unclear why there is an offset of action and different numbing effect duration between these two drugs. In this work, we investigate the thermodynamic cause of such a difference on the anaesthetic effects of the ionised forms of lidocaine and bupivacaine. We applied the Membrane Multi-Phase Solvation Model (MMPSM) to estimate the free energy and partition coefficient of transferring the drugs from the aqueous environment to the membrane interior. The thermodynamic analysis shows that lidocaine diffuses into the membrane faster (higher probability), but bupivacaine takes longer to diffuse outside the membrane (lower probability). These results provide a plausible explanation of the differences in the anaesthesia onset and duration.

KEYWORDS:

• Thermodynamic integration
• membrane model
• membrane-molecule interactions

Abbreviations:

• BC: bupivacaine
• LA: local anaesthetic
• LC: lidocaine
• MD: moleculardynamics
• MMPSM: membrane multi-phase solvation model

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was partially funded by the Consejo Nacional de Ciencia y Tecnología México [grant numbers 178749 and 285642 to A.G.-G., and 132376 to M.C.-T.], Fondo Sectorial de Investigación para la Educación México [grant number A1-S-17041 to M.C.-T.], and Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional México (project number 20202248 to J.M.F.-G.).