Neuromuscular blockade refers to the inhibition of the effective, coordinated contraction of muscles leading to veritable paralysis—either flaccid (i.e., soft) or spastic (i.e., rigid).1 Neuromuscular blocking agents may be classified into those which induce paralysis via depolarization of cells involved in the pathway leading to coordinated muscular contraction and those which inhibit coordinated muscular contraction via processes not involving depolarization. Neuromuscular blockade specifically targets skeletal muscle over smooth muscle, preventing the harmful effects of disrupting smooth muscle function.
Nondepolarizing neuromuscular blocking agents function by binding to the alpha subunit of the nicotinic receptors located on the post-synaptic membrane of the motor end plate. Effectively, this results in flaccid paralysis. The pathophysiology of this effect is that acetylcholine, which is released from the pre-synaptic membrane, can no longer bind to the alpha subunit at the motor endplate, which facilitates coordinated skeletal muscle contraction. When the drug binds to the alpha subunit, competitive inhibition, or a competition to interact with the binding site, prevents activation of the entire unit—a characteristic result of the binding of nondepolarizing neuromuscular blocking agents.1
By preventing of an influx of potassium or other positively-charged ions, these agents prohibit depolarization (i.e., an increase in the charge of a cell relative to its external surroundings, which enables the propagation of a signal along a nerve as it leads to contraction). There are two major classes of these drugs: aminosteroids (e.g., vecuronium, pancuronium, rocuronium) and benzylisoquinoliniums (e.g., mivacurium, cisatracurium, atracurium).1
Succinylcholine is a depolarizing neuromuscular blocker, meaning it binds to the alpha subunit and facilitates propagation of the electrochemical signal which ultimately results in skeletal muscle contraction.2 Succinylcholine is a molecule composed of two conjoined acetylcholine molecules. While it is short acting, the dual molecular structure makes it difficult to degrade, and its molecular structure, which is similar to that of the typical agonist, acetylcholine, results in its ability to render effect when binding to the alpha subunit.2
The two predominant types of acetylcholine receptors are nicotinic and muscarinic. For the most part, the latter facilitates smooth muscle contraction (i.e., involuntary contraction and relaxation of the intestines and blood vessels). Meanwhile, the former facilitates intentional contraction and relaxation of skeletal muscles.3 Since neuromuscular blocking agents alter the interactions of acetylcholine with the alpha subunit on nicotinic receptors, the resulting blockade only affect the functions of skeletal muscles and not those of involuntary, smooth muscle.4
Neuromuscular blocking agents may be divided into those which exert their effects through skeletal muscle contracture and those who exert their effects through skeletal muscle flaccid paralysis. Their function is dictated by their structure, and further subclassification is also applicable. However, both classes bind to the alpha subunit of the nicotinic acetylcholine receptor, meaning that only muscle which contains these receptors (i.e., skeletal muscle) is affected. Therefore, skeletal muscle contraction is impacted by neuromuscular blockade, while smooth muscle function remains unaffected.
References
1. Adeyinka A, Layer DA. Neuromuscular Blocking Agents. In: StatPearls. StatPearls Publishing; 2025. Accessed November 15, 2025. http://www.ncbi.nlm.nih.gov/books/NBK537168/
2. Hager HH, Patel P, Burns B. Succinylcholine Chloride. In: StatPearls. StatPearls Publishing; 2025. Accessed November 15, 2025. http://www.ncbi.nlm.nih.gov/books/NBK499984/
3. Carlson AB, Kraus GP. Physiology, Cholinergic Receptors. In: StatPearls. StatPearls Publishing; 2025. Accessed November 15, 2025. http://www.ncbi.nlm.nih.gov/books/NBK526134/
4. Appiah-Ankam J, Hunter JM. Pharmacology of neuromuscular blocking drugs. Contin Educ Anaesth Crit Care Pain. 2004;4(1):2-7. doi:10.1093/bjaceaccp/mkh002