Tetanic Fade During Partial Transmission Failure Produced by Non-Depolarizing Neuromuscular Blocking Drugs in the Cat

Abstract

1. A comparison has been made of the effects of three acetylcholine antagonists--hexamethonium, tubocurarine and pancuronium--on maximal tetani of limb muscles of cats under chloralose anaesthesia. In most experiments, the indirectly stimulated soleus muscle was studied, but observations were also made on the tibialis anterior and flexor digitorum longus muscles. 2. When neuromuscular block was produced by intra-arterial injections of the acetylcholine antagonists, tetanic tension, though depressed in amplitude did not wane and there was little or no post-tetanic relief of the block as judged by the amplitude of subsequent twitches. On the other hand, during similar degrees of block produced by intravenous injections, tetanic tension rapidly waned, and, after the tetanus, transmission was temporarily facilitated, as evidenced by an increase in the amplitude of post-tetanic twitches. 3. Intravenously injected hexamethonium caused complete waning of tetanic tension in doses too small to depress twitch amplitude and which caused only a small depression of peak tetanic tension. In contrast, pancuronium caused only partial tetanic fade even in doses that produced pronounced depressions of twitch and tetanic tensions. The effects of tubocurarine fell between these extremes. 4. The results suggest that depression of peak tension and tetanic fade are independent effects of acetylcholine antagonists. It is postulated that the former is a consequence of block of post-junctional cholinoceptors, whereas the latter arises from an action of pre-junctional cholinoceptors. 5. The results obtained, together with those of other workers, led to the suggestion that transmitter acetylcholine, in addition to evoking the endplate potential, acts on the nonmyelinated nerve terminals in a positive feed-back mechanism that mobilizes transmitter to keep pace with release during high frequencies of stimulation.

Multiple effects of α‐toxins on the nicotinic acetylcholine receptor

“…Others have suggested that the binding site involved in the production of fade could be a presynaptic AChR [2][3][4][5][6][7][8]. In evaluation of our data it is important to underscore the fact that all efforts to detect interaction or binding of o~-toxins to putative presynaptic ACh receptors of any type have been unsuccessful [11].…”

“…Curare induces a waning or fade in muscle compound action potential (CAP) and tetanus during repetitive nerve stimulation [1]. It has been proposed that fade is caused in part by a presynaptic effect of curare [2][3][4][5][6][7][8]. Reports that or-toxins do not cause fade as does curare [5,6,9,10] and do not bind to the presynaptic nerve terminal [11] have been cited as support for this theory [2,5,9].…”

“…In the past it has been assumed that there is a normal rundown in the release of ACh during high-frequency nerve stimulation and that the addition of AChR blockade by curare induces failure of neurotransmission [13]. Another theory [3] suggests that in addition to postsynaptic AChR block, curare blocks a presynaptic AChR which normally functions to facilitate ACh release during repetitive stimulation (positive feedback). This pre-synaptic effect could account for curareinduced fade in end-plate potentials during repetitive stimulation.…”

Train-of-four fade and neuromuscular block in rats: a comparison between pancuronium, vecuronium, and rocuronium

“…10 A block by non-depolarizing NBAs would lead to a progressive decrease in the amount of ACh released per stimulus during TOF stimulation, accounting for the TOF fade phenomenon. 8,17,18 Based on this mechanism, differences among drugs in the production of the TOF fade can be accounted for by different affinities for prejunctional receptors, i.e. , the greater the affinity, the greater the TOF fade.…”

“…[3][4][5][6] While nondepolarizing NBAs act mainly at the postjunctional site, some investigators have suggested that they also have a prejunctional effect that is responsible for the TOF fade. [7][8][9][10][11] Consequently, drug-dependent differences in TOF fade are believed to be a function of their prejunctional potency. 5,10,[12][13][14] However, Storella et al .…”