The voltage-dependent sodium channel, which mediates the muscle action potential, is also time dependent: prolonged depolarization inactivates the action potential. This can be reversed only by a repolarization of the membrane. By keeping the acetylcholine channel open, the just-mentioned depolarizing blockers keep the muscle membrane depolarized and refractory to impulse initiation. Hemicholinium weakens neuromuscular transmission by blocking the reuptake of choline, thus reducing the synthesis of acetylcholine.

Some drugs strengthen neuromuscular transmission. Acetylcholine agonists, such as nicotine, react directly with the acetylcholine receptor. Others, such as physostigmine, pyridostigmine bromide, and edrophonium chloride, inhibit acetylcholinesterase and strengthen transmission by delaying the breakdown of acetylcholine. The action of physostigmine and pyridostigmine bromide persists for hours, and these agents are used to treat the neuromuscular disease myasthenia gravis; edrophonium chloride, on the other hand, is short acting and is used in diagnosing the disease.