Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N⁺ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.

Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine is more resistant to hydrolysis by cholinesterases, they produce a prolonged depolarization that causes neuromuscular blockade and muscle paralysis. Adding cholinesterase inhibitors further enhances their effects instead of terminating their response, as seen with nondepolarizing blockers.

The effect of depolarizing blockers usually lasts 5-10 minutes. They are often used during an emergency for airway management, endotracheal intubation, or electroconvulsive shock therapy. However, succinylcholine should be avoided for patients with mutated cholinesterases or cholinesterase deficiency, as it can produce more prolonged neuromuscular blockade than desired.