Depolarizing blockers depolarize plasma membranes of skeletal muscle fibers and induce muscle paralysis. They have a rapid onset, usually within a minute, and are helpful for endotracheal intubation, mechanical ventilation, and other surgical procedures.

Succinylcholine, the most widely used depolarizing blocker, resembles the endogenous ligand acetylcholine. It binds to the nicotinic acetylcholine receptors at the motor end plates and induces the opening of the sodium channel, allowing ion entry and membrane depolarization.

Unlike acetylcholine which is readily hydrolyzed, succinylcholine is resistant to hydrolysis by acetylcholinesterase and remains bound to the receptor longer. As membrane depolarization persists, phase I  blockade begins. Neurons stop firing, and the motor endplate fails to repolarize immediately, resulting in involuntary muscle twitching.

After prolonged depolarization,  succinylcholine diffuses away, and the sodium channels close, allowing the membrane to repolarize. Receptors become desensitized to acetylcholine binding, preventing membrane depolarization. This leads to phase II blockade, and the muscles become fully paralyzed.