Other Antagonists of Nondepolarizing Neuromuscular Blockade

Work is ongoing with a completely novel type of antagonist. This compound, ORG 25969 ( Fig. 13-32 ), is a γ-cyclodextrin.^{[649] [650] [651] [652]} It is highly water soluble with a hydrophobic cavity that can encapsulate steroidal neuromuscular blocking drugs.^{[649] [650] [651] [652]} ORG 25969 exerts its effect by forming tight complexes with steroidal neuromuscular blocking drugs (rocuronium > vecuronium ≫ pancuronium),^{[649] [650] [651] [652]} and in so doing, the neuromuscular blocker is no longer available to bind with the acetylcholine receptor. ORG 25969 acts as a chelating agent, and it has no effect on acetylcholinesterase. This property eliminates the need for anticholinergic drugs. The compound's efficacy as an antagonist does not appear to rely on renal excretion of the cyclodextrin-relaxant complex.^[653] Although a change in acid-base status will affect anticholinesterase activity, it does not appear to influence the efficacy of ORG 25969.^[654] In male volunteers, administration of 8 mg/kg ORG 25969 3 minutes after

Figure 13-32 Structure of the synthetic γ-cyclodextrin (ORG 25969).

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