2-O-substituted cyclodextrins as reversal agents for the neuromuscular blocker rocuronium bromide

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 gamma-CD with 4-carboxybenzyl resulted in a CD host molecule I that forms a 1:1 binary complex with rocuronium bromide (K-a 6.2 x 10(5) 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 I was found to exert potent reversal activity (ED50 0.21 mumol/kg, iv) against rocuronium-induced neuromuscular block, and thus proved the viability of using host molecules as antidotes of a biologically active compound. (C) 2002 Elsevier Science Ltd. All rights reserved.