Difference of train-of-four fade induced by nondepolarizing neuromuscular blocking drugs: a theoretical consideration on the underlying mechanisms

Nondepolarizing neuromuscular blocking drugs induce train-of-four (TOF) fade, i.e., the reduction of the fourth to the first twitch height in a train under TOF stimulation. It has been observed that the degree of TOF fade varies with the drug used and is inversely correlated with the potencies of the drug. In this study, the cause of difference of TOF fade was considered using a dynamic model. The model was based on the following assumptions: (1) Twitch response is evoked by the binding of acetylcholine (ACh) molecules to the postsynaptic nicotinic receptors in a neuromuscular junction, (2) time-dependent ACh mobilization in a motor nerve terminal results in less ACh output at the fourth stimulus in a train than at the first stimulus, (3) the drugs compete with ACh for the postsynaptic receptors and inhibit the receptor-binding of ACh, and (4) the drugs have various affinities for the receptors. This study suggested that the difference of affinities of the drugs for postsynaptic ACh receptors may cause the difference of TOF fade.