GOAL To examine in a model of neuromuscular transmission the interaction between two non-depolarizing muscle relaxants. An additive or a supra-additive interaction was evaluated as a function of the affinities of acetylcholine and the muscle relaxants for the two binding sites at a single receptor. METHODS Affinity of acetylcholine for site1 was postulated to be higher than for site2. Muscle relaxants may display a similar pattern of affinities, a higher affinity for site2, or the affinities may be identical. Receptors with both sites occupied by acetylcholine are activated and, if their concentration at an end plate surpasses the critical threshold, initiate contraction of the associated muscle fiber. The number of contracting muscle fibers determines twitch strength of the whole muscle. Neuromuscular block (NMB) = 1--twitch. NMB was simulated for muscle relaxants acting as single agents or in three types of combinations. (a) Complementary fractions of equieffective concentrations. (b) Variable combinations of equieffective concentrations producing NMB equal to NMB produced by the single muscle relaxant (isobolographic analysis), and (c) NMB-vs.-concentration relationship of single agents and of their combination in a fixed ratio. RESULTS Additive interaction was simulated for pairs of muscle relaxants displaying identical ratios of affinities. All other pairs produce a supra-additive interaction, more prominent, the more divergent the patterns of affinities. The slopes of NMB-vs.-concentration curves were steeper for supra-additive combinations than for single agents. CONCLUSION The simulations define conditions leading to additive or supra-additive interaction and suggest an experimental design suitable to test the results.

中文翻译：

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两种非去极化肌肉松弛剂之间相互作用的模拟：累加或超累加的神经肌肉阻滞的产生。

目标在神经肌肉传递模型中检查两种非去极化肌肉松弛剂之间的相互作用。根据乙酰胆碱和肌肉松弛剂对单个受体上两个结合位点的亲和力来评估加性或超加性相互作用。方法假定乙酰胆碱对站点1的亲和力高于对站点2的亲和力。肌肉松弛剂可能显示相似的亲和力模式，对site2的亲和力更高，或者亲和力可以相同。具有乙酰胆碱占据的两个位点的受体被激活，并且如果它们在终板上的浓度超过临界阈值，则引发相关肌纤维的收缩。收缩肌纤维的数量决定了整个肌肉的抽搐强度。神经肌肉阻滞（NMB）= 1-抽搐。针对肌肉松弛剂作为单一药物或以三种类型的组合进行了NMB模拟。（a）等效浓度的互补分数。（b）产生NMB的等效浓度与单一肌肉松弛剂产生的NMB相等的可变组合（等效线描图分析），以及（c）单个药剂及其组合以固定比例的NMB与浓度的关系。结果模拟了成对的肌肉松弛剂的相加相互作用，它们显示出相同的亲和力比。所有其他对都产生超加性相互作用，亲和力模式越突出，越突出。超添加剂组合的NMB与浓度曲线的斜率比单一药剂的陡峭。