Highly Water-Soluble Cucurbit[8]uril Derivative as a Broad-Spectrum Neuromuscular Block Reversal Agent.

J Med Chem

Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, 2205 Songhu Road, Shanghai 200438, China.

Published: December 2022

AI Article Synopsis

  • Researchers have developed a water-soluble cucurbit[8]uril (CB[8]) derivative that effectively reverses neuromuscular block induced by various agents, including benzylisquinolinium and aminosteroid types.
  • The CB[8] derivative shows strong binding affinity in lab tests and significantly reduces recovery time in animal studies, outperforming traditional reversal agents like neostigmine.
  • Toxicity tests indicate that this CB[8] derivative is highly biocompatible and safe, with a maximum tolerance dose of 960 mg/kg.

Article 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 10 M. 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.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.2c01677DOI Listing

Publication Analysis

Top Keywords

cb[8] derivative
16
neuromuscular block
12
highly water-soluble
8
water-soluble cucurbit[8]uril
8
derivative broad-spectrum
8
broad-spectrum neuromuscular
8
block reversal
8
reversal agent
8
derivative
5
cucurbit[8]uril derivative
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!