Nicotinic antagonists used as muscle relaxants

Both pancuronium and d-tubocurarine act by binding to the NAR in a way competitive with acetylcholine. In both cases, the presence of both positive charges is important for activity. Yet, it is questionable whether both cationic groups bind simultaneously to the two acetylcholine binding sites found (at the two a chains) of the NAR, since the distance between those should substantially exceed the one between the two charges in the antagonist molecules. 

The membrane stays partially depolarized during the presence of the agonist. If all receptors were fixed in the inactivated state, the membrane should be completely repolarized. 

If muscle cells have been cut off from their neural input for a couple of weeks, they will express larger numbers of NAR molecules, even outside those membrane regions that were previously in contact with the nerve cells. If acetylcholine or another depolarizing agent is applied to these cells, they will respond with maximum contraction, and no blockade will ensue. Thus, some regulatory mechanism that suppresses muscle contraction upon sustained membrane depolarization in normal cells seems to be lost concomitantly with the denervation. 

Succinylcholine has a more sustained action at the motor endplate than acetylcholine has because it is insensitive to the acetylcholinesterase found in the S5uiapse. There is, however, a second variety of cholinesterase that circulates in the blood plasma, also referred to as butyryl-cholinesterase, which cleaves succinylcholine within minutes. This moderately rapid inactivation makes it possible to control the degree of muscle relaxation by adjusting the infusion rate of the agent after discontinuation, the remaining succinylcholine will be swiftly hydrolysed, and the block will subside  

Maximal release of acetylcholine by the motoneurons occurs in tetanus, due to the toxin-mediated inactivation of glycinergic neurons that normally inhibit them. This results not in blockade but maximal muscle activity, so strong that bone fractures are commonly observed. However, blockade can be observed with inhibitors of acetylcholine esterase (see below). 

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