2-O-Substituted Cyclodextrins as Reversal Agents for the Neuromuscular Blocker Rocuronium Bromide Original Research Article

A series of secondary face modified cyclodextrins (CDs) were synthesised with the aim of constructing host molecules capable of forming host–guest complexes with neuromuscular blockers, especially with rocuronium bromide. Perfacial 2-O-substitution of γ-CD with 4-carboxybenzyl resulted in a CD host molecule 1 that forms a 1:1 binary complex with rocuronium bromide (Ka 6.2×105 M−1). The biological activities of this compound and other derivatives as reversal agents of rocuronium bromide were examined in vitro (mouse hemi-diaphragm) and in vivo (anaesthetized guinea pigs). The host molecule 1 was found to exert potent reversal activity (ED50 0.21 μmol/kg, iv) against rocuronium-induced neuromuscular block, and thus proved the viability of using host molecules as antidotes of a biologically active compound.