Abstract：
Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 107 M-1. In vivo studies demonstrate that the administration of the CB[8] derivative could significantly accelerate the recovery time compared to the placebo or neostigmine groups. The reversal activity of the CB[8] derivative is comparable to or higher than that of clinically approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative displays outstanding biocompatibility, with the maximum tolerance dose as high as 960 mg kg-1.
摘要：
广谱剂对于逆转神经肌肉阻断剂诱导的残余curarization具有重要意义。这里,我们报道了一种高水溶性葫芦[8]脲(CB[8])衍生物,作为一种广谱神经肌肉阻滞逆转剂,其由苄基半烯啉和氨基类固醇神经肌肉阻滞剂通过超分子螯合策略诱导.UV/Vis竞争滴定试验表明，CB[8]衍生物对苄烯醇型顺式阿曲库铵和氨基类固醇型罗库溴铵的高结合亲和力，维库溴铵,和潘库溴铵,在107M-1的水平。体内研究表明，与安慰剂或新斯的明组相比，CB[8]衍生物的给药可以显着加快恢复时间。CB[8]衍生物的逆转活性与临床批准的sugammadex相当或更高。急性毒性评估表明，CB[8]-衍生物表现出优异的生物相容性，最大耐受剂量高达960mgkg-1。
