History of the development of antagonists for neuromuscular blocking agents

Muscle relaxation induced by neuromuscular blocking agents (NMBAs) is necessary for tracheal intubation and immobilization during surgery. Although acetylcholinesterase inhibitors have been successfully used as antagonists for NMBAs, they have their limitations; their effects are transient and ineffective against profound neuromuscular blockade. In the past, alternative antagonists were developed, such as germine and 4-aminopyridine, which are effective for the treatment of diseases causing muscle weakness and could potentially be used as antagonists for NMBAs. Unfortunately, these drugs did not come into practical use due to unwanted side-effects. Sugammadex is an almost ideal antagonist because it rapidly forms a rigid complex with rocuronium and produces less adverse effects. The development of novel NMBAs and antagonists, especially sugammadex, has revolutionized anesthesia practice. Recently, novel short-acting NMBAs, such as gantacurium and CW002 have been developed. Their effects can be reversed by the amino-acid l-cysteine. More recently, calabadions have been developed, which can form complexes with both steroidal and bisbenzyl-isoquinolinium NMBAs, in a similar fashion as sugammadex. Understanding the history of the NMBA antagonist’s development is interesting and useful for modern anesthesiologists since it enhances their knowledge about the mechanisms involved in neuromuscular transmission and might lead to the development of ideal NMBA antagonists.