Novel neuromuscular blocking drugs and antagonists.

PURPOSE OF REVIEW: This review summarizes recent progress in the development of new muscle relaxants that are inactivated by cysteine, and considers the evolving paradigm of selective relaxant binding or degrading agents that can reverse neuromuscular blockade at any time. RECENT FINDINGS: The benzylisoquinoline compound gantacurium is a nondepolarizing muscle relaxant with an ultrashort duration largely determined by the rapid rate at which endogenous L-cysteine binds to, and permanently inactivates, the molecule. Although the clinical development of gantacurium has been hampered by modest histamine release, preclinical studies demonstrating that the drug can be rapidly reversed by injecting L-cysteine led to the development of CW002, an intermediate duration molecule that can also be reversed at any time by L-cysteine injection. Clinical trials with CW002 are now underway. The ability to reverse complete paralysis with cysteine dovetails with the established selective aminosteroid binding agent sugammadex, and the recently described universal relaxant binding agent calabadion. Taken together, the concept of rapid reversal at any time raises the question of whether an ultrashort nondepolarizing drug is needed if safe and cost-effective relaxant binding agents are available. SUMMARY: The gantacurium derivative CW002 is an intermediate duration, nondepolarizing, cysteine-inactivated, neuromuscular blocking drug currently in clinical trials. Like sugammadex reversal of rocuronium, CW002 can be reversed at any time by cysteine injection.

Sugammadex in clinical practice.

The availability of sugammadex allows greater flexibility in the use of rocuronium and vecuronium during anaesthesia and surgery. The neuromuscular block induced by both drugs can be reversed from both superficial and deep levels of block by adjusting the dose of sugammadex. The dose of sugammadex for reversal of shallow block produced by these neuromuscular blocking drugs is approximately 2 mg.kg(-1) and for deep block the dose is 4 mg.kg(-1). A larger dose of sugammadex (16 mg.kg(-1)) administered 3 min after the neuromuscular blocking drug allows rapid reversal of a neuromuscular block induced by 1-1.2 mg.kg(-1) of rocuronium, thereby raising the possibility of using rocuronium as a replacement for suxamethonium. The use of sugammadex has not been reported to be associated with recurrence of block provided a dose that is adequate for reversal has been used. Sugammadex appears to have an acceptable safety profile. There are no requirements for dose adjustment for age or the use of potent volatile anaesthetic agents.