The effect of local anesthetics on the inhibition of adult muscle-type nicotinic acetylcholine receptors by nondepolarizing muscle relaxants

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 10 µM 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 45.5 µM and 11.1 µM, 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.