Efficient Reversal\nof Neuromuscular Blocking Agent-Induced\nBiological Functions and Side Effects by an Extended Biphen[3]arene\nCarboxylate

Neuromuscular blocking agents (NMBAs) are widely administered\nduring\nanethesia to prevent the patient from moving and optimize surgical\nconditions. Timely reversal of the muscle relaxation state induced\nby NMBAs at the end of surgery is necessary to recover autonomous\nrespiration and muscle function. Herein, an extended biphen[3]arene\ncarboxylate (ExBP3C) was designed and synthesized by a supramolecular\nsequestration approach as a reversal agent with high efficiency and\ngenerality against several representative NMBAs. ExBP3C exhibited\nrobust host–guest complexation toward atracurium, rocuronium,\nvecuronium, pancuronium, and gallamine with an association constant\nof up to 10<sup>8</sup> M<sup>–1</sup>. A series of in vitro\nand in vivo safety tests preliminarily demonstrated that this synthetic\nmacrocycle had good biocompatibility. Compared to sugammadex, post-treatment\nby an equivalent dose of ExBP3C could produce a more efficient reversal\nfunction. Additionally, a single dose of such a reversal agent was\nalso able to completely recover overdose atracurium-induced heart\nrate abnormalities within 2 min.