Neuromuscular blocking agents

Blockade of transmission at the nmj is used during surgery to generate relaxation of skeletal muscle. They are effective in one minute of injection. Muscle relaxant drugs fall into two class depending on their mode of action and all contain a structural resemblance to ACh.Nondepolarizing drugs like the tetrahydroisoquinoline derivatives (example, the prototypical d-tubocurarine, atracurium) and the aminosteroids (example, pancuronium), are competitive antagonists of nAChR. The duration of action of such drugs ranges from 15 to 180 minutes. Their action can be quickly reversed by AChE inhibitors, like neostigmine, which cause a rise in the concentration of ACh that then out-competes the drug for the nicotinic receptor.

Depolarizing drugs, of that succinylcholine is the only agent of clinical significance, are nAChR agonists. At first, agonist binding opens the nicotinic receptor channel causing persistent depolarization of the endplate. This primary causes generalized disorganized contractions of muscles known as fasciculations, and is followed by the flaccid paralysis as muscle Ca²⁺ channels inactivate and the contraction mechanism fails as an outcome. This early stage in the action of depolarizing drugs (known as phase I block) occurs as a result of an ACh-like depolarization and therefore is augmented instead of reversed by AChE inhibitors. With enduring exposure phase II block takes place in which the nAChR either de-sensitizes, or suffers open channel blockade by the drug. The phase II block can be reversed by AChE inhibitors. Succinylcholine is quickly hydrolyzed by circulating esterases; therefore its duration of action is only about 5 minutes.