Department of Dental Basic Education, Asahi University School of Dentistry, Gifu, Japan.
Anesth Analg. 2012 Feb;114(2):310-2. doi: 10.1213/ANE.0b013e31823ed410. Epub 2011 Dec 9.
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.
局部麻醉药能否在临床相关浓度下与膜脂质相互作用，从而表现出对映异构体的差异仍存在疑问。我们比较了布比卡因对映异构体在含有心磷脂和胆固醇的仿生膜中的作用。布比卡因在心脏毒性 5 μM 时与膜相互作用，其效力为 S(-)-对映体<外消旋体< R(+)-对映体，这与它们的心脏毒性顺序一致。随着药物浓度的降低，这种差异变得更大，这可能解释了先前报道的布比卡因对映异构体心脏毒性效力不一致的原因。与生物膜的相互作用可能部分解释了局部麻醉药的作用模式。
