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Novel neuromuscular blocking drugs and antagonists

Heerdt, Paul M.a; Sunaga, Hiroshib; Savarese, John J.c

Current Opinion in Anaesthesiology: August 2015 - Volume 28 - Issue 4 - p 403–410
doi: 10.1097/ACO.0000000000000209
DRUGS IN ANESTHESIA: Edited by Tong J. Gan
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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.

aWeill Medical College of Cornell University, Department of Anesthesiology, and Department of Anesthesiology/Critical Care Medicine, Memorial Sloan-Kettering Cancer Center

bJikei University School of Medicine

cWeill Medical College of Cornell University, New York, New York, USA

Correspondence to Paul M. Heerdt, MD, PhD, 525 East 68th Street, Ladson 2, Box 50, New York, NY 10021, USA. Tel: +1 212 746 2701; fax: +1 212 746 8316; e-mail: pmheerd@med.cornell.edu

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