Nonclassic and Noncompetitive Actions of Neuromuscular Drugs

Several drugs can interfere with the receptor, directly or through its lipid environment, to change transmission. These drugs react with the neuromuscular receptor to change its function and to impair transmission but do not act through the acetylcholine-binding site. These reactions cause drug-induced changes in the dynamics of the receptor, and instead of opening and closing sharply, the modified channels are sluggish. They open more slowly and stay open longer, or they close slowly and in several steps, or both. These effects on channels cause corresponding changes in the flow of ions and distortions of the end-plate potential. The clinical effect depends on the molecular events. For example, procaine, ketamine, inhaled anesthetics, or other drugs that dissolve in the membrane lipid may change the opening or closing characteristics of the channel.^{[52] [53]} If the channel is prevented from opening, transmission is weakened. If, however, the channel is prevented from or slowed in closing, transmission may be enhanced. These drugs do not fit the classic model, and the impaired neuromuscular function is not antagonized by increasing perijunctional acetylcholine concentrations with cholinesterase inhibitors. Such drugs can be involved in two clinically important reactions: receptor desensitization and channel blockade. The former occurs in the receptor molecule, and the latter occurs in the ion channel.