Paul Matthias, Fokt Ralf M, Kindler Christoph H, Dipp Natalie C J, Yost C Spencer
Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143, USA.
Anesth Analg. 2002 Aug;95(2):362-7, table of contents. doi: 10.1097/00000539-200208000-00022.
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.
Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors.
挥发性麻醉药可增强非去极化肌松药（NDMRs）产生的神经肌肉阻滞作用。神经肌肉接头被认为是这种相互作用的发生部位。我们检验了这样一个假说，即挥发性麻醉药增强肌肉松弛作用是药物对烟碱型乙酰胆碱受体联合作用的结果。成年小鼠肌肉烟碱型乙酰胆碱受体（α(2)、β、δ、ε）在非洲爪蟾卵母细胞中进行异源表达。建立了维库溴铵、d -筒箭毒碱、异氟烷和七氟烷对乙酰胆碱诱导电流抑制作用的浓度 - 效应曲线。随后，在挥发性麻醉药存在的情况下，以相当于单独产生50%抑制作用浓度一半的浓度研究了NDMRs的抑制作用。所有单独测试的化合物均产生快速且易于逆转的浓度依赖性抑制作用。维库溴铵、d -筒箭毒碱、异氟烷和七氟烷的计算50%抑制浓度值分别为9.9 nM（95%置信区间[CI]，8.4 - 11.4 nM）、43.4 nM（95% CI，33.6 - 53.3 nM）、897 μM（95% CI，699 - 1150 μM）和818 μM（95% CI，685 - 1001 μM）。异氟烷或七氟烷与维库溴铵和d -筒箭毒碱共同应用时，显著增强了它们的抑制作用，在低浓度NDMRs时尤其如此。挥发性麻醉药可能通过增强拮抗剂在受体部位的亲和力来增加NDMRs的效能。这种效应可能有助于临床上观察到的挥发性麻醉药增强神经肌肉阻滞作用。
异氟烷和七氟烷增强非去极化肌松药对烟碱型乙酰胆碱受体的受体阻断作用。
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