Volatile anesthetics enhance the neuromuscular blockade produced by 
nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a 
postulated site of this interaction. We tested the hypothesis that volatile 
anesthetic enhancement of muscle relaxation is the result of combined drug 
effects on the nicotinic acetylcholine receptor. The adult mouse muscle 
nicotinic acetylcholine receptor (alpha(2), beta, delta, epsilon) was 
heterologously expressed in Xenopus laevis oocytes. Concentration-effect curves 
for the inhibition of acetylcholine-induced currents were established for 
vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, 
inhibitory effects of NDMRs were studied in the presence of the volatile 
anesthetics at a concentration equivalent to half the concentration producing a 
50% inhibition alone. All individually tested compounds produced rapid and 
readily reversible concentration-dependent inhibition. The calculated 50% 
inhibitory concentration values were 9.9 nM (95% confidence interval [CI], 
8.4-11.4 nM), 43.4 nM (95% CI, 33.6-53.3 nM), 897 microM (95% CI, 699-1150 
microM), and 818 microM (95% CI, 685-1001 microM) for vecuronium, 
d-tubocurarine, isoflurane, and sevoflurane, respectively. Coapplication of 
either isoflurane or sevoflurane significantly enhanced the inhibitory effects 
of vecuronium and d-tubocurarine, especially so at small concentrations of 
NDMRs. Volatile anesthetics increase the potency of NDMRs, possibly by enhancing 
antagonist affinity at the receptor site. This effect may contribute to the 
clinically observable enhancement of neuromuscular blockade by volatile 
anesthetics.
IMPLICATIONS: Isoflurane and sevoflurane enhance the receptor blocking effects 
of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors.