Development of New Neuromuscular Blocking Agents

Abstract

Increased understanding of structure–activity relationships has allowed the development of neuromuscular blocking compounds and reversal agents that are unique and offer pharmacokinetic and dynamic improvements over their predecessors. Compounds have been developed that have a short duration of effect, a rapid clearance and a decrease in adverse effects. The fumarates comprise one of the series of compounds that have resulted from this research. These compounds are inactivated through a mechanism that is completely new for neuromuscular blocking agents—that of cysteine adduction. The work has also led to the development of alternative ways to enhance recovery of neuromuscular function. Sugammadex encapsulates steroidal neuromuscular blocking compounds making them unable to interact with the acetylcholine receptor and reversing their effect within minutes. Recovery from gantacurium- or CW002-induced neuromuscular block can be shortened by administration of l-cysteine. These new neuromuscular blocking and reversal agents allow for maintenance of an adequate depth of neuromuscular block intraoperatively and almost immediate recovery of neuromuscular function, a sensible goal as the risks of residual neuromuscular block are increasingly appreciated.