Highly Water-Soluble Cucurbit[8]uril Derivative as a Broad-Spectrum Neuromuscular Block Reversal Agent

Broad-spectrum
agents for the reversal of residual curarization
induced by neuromuscular blocking agents are of great significance.
Here, we report a highly water-soluble cucurbit[8]­uril (CB[8]) derivative
as a broad-spectrum neuromuscular block reversal agent induced by
both benzylisquinolinium and aminosteroid neuromuscular block agents
by the supramolecular sequestration strategy. The UV/Vis competition
titration assays suggest the high binding affinity of the CB[8] derivative
toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type
rocuronium, vecuronium, and pancuronium, at the level of 107 M–1. In vivo studies demonstrate that the administration
of the CB[8] derivative could significantly accelerate the recovery
time compared to the placebo or neostigmine groups. The reversal activity
of the CB[8] derivative is comparable to or higher than that of clinically
approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative
displays outstanding biocompatibility, with the maximum tolerance
dose as high as 960 mg kg–1.