Nondepolarizing neuromuscular blockers bind to the nAChR on the motor end plate to prevent membrane depolarization and muscular contractions. Most nondepolarizing blockers resemble the endogenous ligand ACh, and so they competitively bind to the nAChR. However, unlike ACh, their bulky structure prevents the conformational changes necessary for receptor activation. As a result, ion channels remain closed, preventing muscle end plate depolarization. This leads to neuromuscular transmission blockade and muscle relaxation. The induced effect can be reversed by administering AChE enzyme inhibitors. They block AChE, and inhibit degradation of ACh elevating its concentration. However, when the nondepolarizing blockers are administered in large doses, they block the sodium channel pore as well. This results in an intense neuromuscular blockade, which is difficult to reverse using AChE inhibitors.