Drugs That Enhance or Block Transmission at the
That Stimulate the Muscle Fiber by Acetylcholine-Like Action.
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.