Prejunctional Actions of Neuromuscular Blocking Drugs

Abstract

The major action of non-depolarizing neuromuscular blocking agents is that they are competitive antagonists at the skeletal muscle postjunctional nicotinic receptor. In addition, they also block acetylcholine receptors in the autonomic nervous system, including muscarinic receptors at the sino-atrial node, and nicotinic receptors at ganglia. As well as blocking the muscle postjunctional nicotinic receptors, large concentrations can produce non-competitive block by occluding the endplate channel itself. The well-known phenomena of tetanic fade and train-of-four fade have been ascribed to a prejunctional action of the compounds. This is controversial. It has been argued that the prime prejunctional effect of, for example, tubocurarine, is to reduce transmitter mobilization. Others have argued that the prime effect is to increase release. This paper describes how different elements of our research effort over the years have led to a hypothesis that attempts to unify some of these apparently contradictory views.