Drugs That Enhance or Block Transmission at the Neuromuscular Junction

Drugs That Enhance or Block Transmission at the Neuromuscular Junction

Drugs That Stimulate the Muscle Fiber by Acetylcholine-Like Action. Many compounds, includingmethacholine, car-bachol, and nicotine, have the same effect on the musclefiber as does acetylcholine. The difference between these drugs and acetylcholine is that the drugs are not destroyed by cholinesterase or are destroyed so slowly that their action often persists for many minutes to several hours. The drugs work by causing localized areas of depolarization of the muscle fiber membrane at the motor end plate where the acetylcholine receptors are located. Then, every time the muscle fiber recovers from a previous contraction, these depolarized areas, by virtue of leaking ions, initiate a new action potential, thereby causing a state of muscle spasm.

Drugs That Stimulate the Neuromuscular Junction by Inactivating Acetylcholinesterase. Three particularly well-known drugs, neostigmine, physostigmine, and diisopropyl fluorophosphate, inactivate the acetyl-cholinesterase in the synapses so that it no longer hydrolyzes acetylcholine. Therefore, with each succes-sive nerve impulse, additional acetylcholine accumu-lates and stimulates the muscle fiber repetitively. This causes muscle spasm when even a few nerve impulses reach the muscle. Unfortunately, it also can cause death due to laryngeal spasm, which smothers the person.

Neostigmine and physostigmine combine with acetyl-cholinesterase to inactivate the acetylcholinesterase for up to several hours, after which these drugs are displaced from the acetylcholinesterase so that the esterase once again becomes active. Conversely, diiso-propyl fluorophosphate, which has military potential as a powerful “nerve” gas poison, inactivates acetyl-cholinesterase for weeks, which makes this a particu-larly lethal poison.

Drugs That Block Transmission at the Neuromuscular Junction. Agroup of drugs known as curariform drugs can prevent passage of impulses from the nerve ending into the muscle. For instance, D-tubocurarine blocks the action of acetylcholine on the muscle fiber acetylcholine recep-tors, thus preventing sufficient increase in permeability of the muscle membrane channels to initiate an action potential.