Competitive Neuromuscular Blocking Drugs

Maclagan, Jennifer

doi:10.1007/978-3-642-45476-9_6

Cited by 19 publications

(12 citation statements)

References 198 publications

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“…Although a priori this frequency of stimulation might seem too low to induce a completely fused tetanic contraction in a fast contracting muscle as is the case of the extensor digitorum longus (Close 1964) used in the present work, it should be recalled that the experiments were performed at room temperature (22 °–24 °). Seeing the Q 10 for the rate of development of tension in skeletal muscles is about 1.5 (Maclagan 1976) the contraction time course is longer in our experimental conditions, compared to the situation at 37 ° (Close 1964). This consequently decreases the frequency of stimulation at which the sequential contractions fuse, leading to a smooth and well sustained 50 Hz generated tetanic contraction (fig.…”

Section: Methodsmentioning

confidence: 55%

Cellular Mechanisms of Atracurium‐Induced Tetanic Fade in the Isolated Rat Muscle

Nascimento

Serra

Oliveira

2004

Basic Clin Pharma Tox

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Although atracurium is a widely used neuromuscular blocker, we still lack knowledge regarding some of its cellular mechanisms of action. Thus, similar to other clinically used blockers atracurium induces, both in vivo and in vitro, fade of the tetanic contraction. However, the cellular mechanisms underlying this tetanic fade have never been systematically studied. In the present work these mechanisms were investigated in vitro. A sciatic nerve extensor digitorum longus muscle preparation of the rat was used. A combination of myographical and electrophysiological techniques was employed. Indirect twitches were evoked at 0.1 Hz and tetanic contractions at 50 Hz. Trains of end-plate potentials were evoked at a frequency of 50 Hz. The electrophysiological variables used in the analysis of the trains of end-plate potentials were: peak amplitude of the first end-plate potential in the train, peak amplitude of plateau end-plate potentials in the train, tetanic run-down of the end-plate potentials' train, quantal content of first and plateau end-plate potentials in the train, quantal size. In the myographical study atracurium, at a concentration of 2.4 mM, induced a complete fade of the tetanic contraction while only slightly affected the twitch. In the electrophysiological study atracurium, at the same 2.4 mM concentration, significantly decreased the amplitude of both first end-plate potentials in the train (control: 14.4 mV; atracurium: 3.2 mV) and plateau end-plate potentials (control: 10.8 mV; atracurium: 2.4 mV) and reinforced the tetanic run-down of the train of end-plate potentials, evaluated as the percent loss in amplitude of plateau end-plate potentials compared to first end-plate potentials in the trains (control: 25.2%; atracurium: 33.2%). Atracurium also significantly decreased the quantal content of first end-plate potentials in the train (control: 231; atracurium: 68), the quantal content of plateau end-plate potentials (control: 159; atracurium: 42) and the quantal size (control: 0.119 mV; atracurium: 0.075 mV). In relative terms the decrease in quantal content was about twice as large as the decrease in quantal size. This indicates that the fade of the tetanic contraction induced by atracurium (2.4 mM) is due to both pre-and postsynaptic blocking effects, the presynaptic one being stronger.

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Section: Methodsmentioning

confidence: 55%

Cellular Mechanisms of Atracurium‐Induced Tetanic Fade in the Isolated Rat Muscle

Nascimento

Serra

Oliveira

2004

Basic Clin Pharma Tox

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“…has been reported previously during the period immediately following a block caused by a single intravenous injection of decamethonium (Vrbova & Maclagan, 1966;Maclagan, 1976).…”

Section: A Utoradiographymentioning

confidence: 57%

Labelled Decamethonium in Cat Muscle

Creese

Maclagan

1976

British J Pharmacology

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I Tritium-labelled decamethonium was infused intravenously in 12 cats at final rates of 1.3-4.2 nmol kg-' min-' to produce a steady plasma concentration which ranged between 0.21-1.3 gimol/l in different experiments. Muscle contractions were elicited by nerve stimulation and the potential at the end-plate regions of superficial fibres was recorded by extracellular electrodes. 2 Under these conditions, it was not possible to obtain a steady degree of neuromuscular block. The initial decrease in muscle contractions was followed by recovery towards the original value although the concentration of decamethonium in the plasma remained constant, or in some cases rose. The initial depolarization of the end-plate region also waned during the constant infusion of the drug. 3 Once the twitch tension had returned to control values during infusion of the drug, prolongation of the infusion for a total of four hours did not produce a secondary neuromuscular block. 4 Scintillation counting showed that during infusion oflabelled decamethonium the radioactivity ofthe muscles increased progressively with time. The uptake was less in the soleus muscle than in the fastcontracting flexor longus digitorum and extensor longus digitorum muscles. Muscles which had been denervated 12-13 days previously showed a greater uptake of labelled drug than control muscles from the contralateral limb. 5The labelled drug was localized by autoradiography of frozen sections of leg muscles following intra-arterial injection of decamethonium. Grain counts in individual fibres showed that small amounts of decamethonium had entered the muscle fibres along their entire length, and there was increased uptake of the drug into the cell in the region of the end-plate. 6 The mechanisms underlying the waning of the pharmacological response during constant application of depolarizing drugs are discussed.

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“…In most mammalian muscles, depolarizing agents induce paralysis (for reviews see Zaimis and Head 1976;MacLagan 1976). As shown in the rat diaphragm, the potency of epibatidine was comparable with that of suxamethonium (Fig.…”

Section: Muscle End Plate Nicotinic Receptorsmentioning

confidence: 79%

Epibatidine: high potency and broad spectrum activity on neuronal and neuromuscular nicotinic acetylcholine receptors

Lembeck

1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The activity of epibatidine at neuronal and neuromuscular nicotinic acetylcholine receptors was investigated in several in situ and in vitro systems and compared with the activity of nicotine and suxamethonium. Activation of ganglionic nicotinic receptors by epibatidine was shown in the guinea-pig ileum (contraction mediated by the cholinergic neurons of the ileum) and in pithed and atropinized rats (rise in blood pressure). Epibatidine also activated nicotinic receptors at the peripheral terminals of afferent C-fibres (rabbit ear) and in the brain (antidiuresis in rats). The agonistic effects of epibatidine were followed by long-lasting receptor desensitization. No antinociceptive effect of epibatidine was seen in rats at a dose free of motor impairment. On muscle end plate nicotinic receptors of the rat diaphragm (not responding to depolarizing agents by contraction), epibatidine was equipotent with suxamethonium in causing neuromuscular inhibition. On an extraocular muscle of the rabbit (responding to depolarizing agents by contraction) epibatidine in vitro and in situ caused a contraction at a 100-fold lower dose than suxamethonium. The Straub tail reaction in mice to epibatidine could be attributed to the sustained stimulation of motor end plate receptors of the "slow contracting" type of muscle fibres by epibatidine. In conclusion epibatidine was the most potent agonist on all neuronal and neuromuscular nicotinic receptors examined.

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Competitive Neuromuscular Blocking Drugs

Cited by 19 publications

References 198 publications

Cellular Mechanisms of Atracurium‐Induced Tetanic Fade in the Isolated Rat Muscle

Cellular Mechanisms of Atracurium‐Induced Tetanic Fade in the Isolated Rat Muscle

Labelled Decamethonium in Cat Muscle

Epibatidine: high potency and broad spectrum activity on neuronal and neuromuscular nicotinic acetylcholine receptors

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