title: 2-O-substituted cyclodextrins as reversal agents for the neuromuscular blocker rocuronium bromide.
abstract: 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 1 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 1 was found to exert potent reversal activity (ED(50) 0.21 micromol/kg, iv) against rocuronium-induced neuromuscular block, and thus proved the viability of using host molecules as antidotes of a biologically active compound.
authors.affiliation: Department of Medicinal Chemistry, Organon Laboratories Ltd., Newhouse, Lanarkshire ML1 5SH, Scotland, UK.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Tarver
authors.forename: Simon J A
authors.initials: SJ
authors.lastname: Grove
authors.forename: Kirsteen
authors.initials: K
authors.lastname: Buchanan
authors.forename: Anton
authors.initials: A
authors.lastname: Bom
authors.forename: Andrew
authors.initials: A
authors.lastname: Cooke
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Rutherford
authors.forename: Ming Qiang
authors.initials: MQ
authors.lastname: Zhang
mesh_terms: D000732:Androstanols / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D003505:Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009126:Muscle Relaxation / Q000187:drug effects; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077123:Rocuronium; D013329:Structure-Activity Relationship
chemical_list: D000732:Androstanols; D003505:Cyclodextrins; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium