Update on neuromuscular pharmacology.
OBJECTIVE
We review the efficacy and safety of gantacurium and AV002, two novel, investigational fumarate-based nondepolarizing neuromuscular blockers, as well as sugammadex and cysteine, two novel reversal drugs that have no acetylcholinesterase inhibition properties.


RESULTS
Gantacurium (with a pharmacodynamic profile similar to that of succinylcholine) and AV002 (with an intermediate duration of action) have shown efficacy in animals and, for gantacurium, in humans. Animal data have shown that exogenous administration of the amino acid cysteine accelerates the natural chemical degradation of both gantacurium and AV002 via the cysteine adduction pathway. Another reversal drug, sugammadex (a modified gamma-cyclodextrin and the first selective relaxant binding agent), forms very tight complexes in a 1: 1 ratio with steroidal neuromuscular blocking agents.


CONCLUSIONS
In a multicenter phase-2 randomized controlled study in the European Union, the efficacy and safety of gantacurium were evaluated, but results have not yet been published. Sugammadex is currently available in the European Union, but the United States Food and Drug Administration has had concerns about its safety (hypersensitivity and allergic reactions) and has asked for additional safety data. It is hoped that the widespread use of sugammadex in the European Union will provide additional information.
Naguib
Mohamed
M
Department of Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. Naguib@mdanderson.org
Brull
Sorin J
SJ
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000493:pharmacokinetics / Q000494:pharmacology*
C542547:CW 002; D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D003545:Cysteine; C451919:gantacurium