Department of Anesthesiology, First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Eur J Pharmacol. 2010 Mar 25;630(1-3):29-33. doi: 10.1016/j.ejphar.2009.12.028. Epub 2010 Jan 4.
The primary action of local anesthetics is to inhibit voltage-gated Na(+) channels. However, local anesthetics also have an inhibitory effect on muscle-type nicotinic acetylcholine receptors. Because local anesthetics could increase the neuromuscular blockade produced by nondepolarizing muscle relaxants, we investigated the interaction of local anesthetics with nondepolarizing muscle relaxants at adult muscle-type nicotinic acetylcholine receptors. This study tested the effects of lidocaine and procaine, alone and in combination with vecuronium and cisatracurium, on adult muscle-type nicotinic acetylcholine receptors. The adult mouse muscle-type nicotinic acetylcholine receptor was expressed in HEK293 cells and activated with 10microM acetylcholine. Currents were recorded using the whole-cell voltage-clamp technique. Adult muscle-type nicotinic acetylcholine receptors were potently inhibited by all the tested compounds. Although the potencies of procaine and lidocaine were statistically significantly different at adult muscle-type nicotinic acetylcholine receptors (50% inhibitory concentration values of 45.5microM and 11.1microM, respectively), procaine and lidocaine enhanced the inhibitory effect of nondepolarizing muscle relaxants at adult muscle-type nicotinic acetylcholine receptors to the same extent. The increased adult muscle-type nicotinic acetylcholine receptor inhibition produced when local anesthetics are combined with nondepolarizing muscle relaxants may contribute to the clinical enhancement of neuromuscular blockade by local anesthetics.
局部麻醉剂的主要作用是抑制电压门控的 Na(+)通道。然而，局部麻醉剂对肌肉型烟碱型乙酰胆碱受体也有抑制作用。由于局部麻醉剂可以增加非去极化肌松剂产生的神经肌肉阻滞作用，我们研究了局部麻醉剂与非去极化肌松剂在成人肌肉型烟碱型乙酰胆碱受体上的相互作用。本研究测试了利多卡因和普鲁卡因单独和与维库溴铵和顺式阿曲库铵联合使用对成人肌肉型烟碱型乙酰胆碱受体的影响。成人肌肉型烟碱型乙酰胆碱受体在 HEK293 细胞中表达，并通过 10μM 乙酰胆碱激活。使用全细胞膜片钳技术记录电流。所有测试化合物均强烈抑制成人肌肉型烟碱型乙酰胆碱受体。虽然普鲁卡因和利多卡因在成人肌肉型烟碱型乙酰胆碱受体上的效力有统计学上的显著差异（半数抑制浓度值分别为 45.5μM 和 11.1μM），但普鲁卡因和利多卡因以相同的程度增强了非去极化肌松剂对成人肌肉型烟碱型乙酰胆碱受体的抑制作用。当局部麻醉剂与非去极化肌松剂联合使用时，增加的成人肌肉型烟碱型乙酰胆碱受体抑制作用可能有助于局部麻醉剂增强神经肌肉阻滞作用的临床效果。
