Anionic Cyclophanes as Potential Reversal Agents of Muscle Relaxants by Chemical Chelation

A series of carboxyl-containing cyclophanes have been designed and synthesised as chemical chelators (or host molecules) of cationic muscle relaxant drugs (or guest molecules). Three of these cyclophane derivatives, 1–3, have been shown by NMR to form 1:1 complexes with the muscle relaxants pancuronium, 4 and gallamine, 5 in D2O, with association constants up to 104 M−1. When tested in an in vitro chick biventer muscle preparation, the cyclophanes reversed the neuromuscular block induced by pancuronium and gallamine, with 3 having the most effective reversal against pancuronium (EC50 40 μM).