Characterization of the interactions between volatile anesthetics and neuromuscular blockers at the muscle nicotinic XXXX receptor.

@entity4094 @entity1238 @entity19 @entity3369 @entity2614 @entity5161 @entity2899 @entity121 @entity934
Volatile anesthetics enhance the @entity4094 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 @entity121 is the result of combined drug effects on the nicotinic @entity934 receptor. The adult @entity19 muscle nicotinic @entity934 receptor (alpha(2), beta, delta, epsilon) was heterologously expressed in @entity1238 oocytes. Concentration-effect curves for the inhibition of @entity934 -induced currents were established for @entity3369 , @entity2899 , @entity5161 , and @entity2614 . 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 @entity3369 , @entity2899 , @entity5161 , and @entity2614 , respectively. Coapplication of either @entity5161 or @entity2614 significantly enhanced the inhibitory effects of @entity3369 and @entity2899 , 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 @entity4094 by volatile anesthetics. IMPLICATIONS: @entity5161 and @entity2614 enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic @entity934 receptors.
