Amide naphthotube as a novel supramolecular sequestration agent for tetracaine and decamethonium

Zhao, Cheng-Da1,2; Cai, Wei3; Chen, Wen-Jie1,2; Yao, Huan1,2; Wang, Song-Meng4; Li, Kailin3; Ma, Yan-Long5,6; Wang, Li-Li1,2; Yang, Liu-Pan1,2

2024

10.7150/thno.93654

THERANOSTICS   影响因子和分区

1838-7640

Rationale: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. Methods: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. Results: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K-a = 1.89x107 M-1) and decamethonium (K-a = 1.01x107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. Conclusion: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.

supramolecular sequestration detoxification tetracaine decamethonium amide naphthotube

SCI

英语

其他

National Natural Science Foundation of China["22174059","22201128","22301046"] ; Natural Science Foundation of Hunan Province, China["2022JJ40363","2022JJ40365"] ; Young Science and Technology Innovation Program of Hunan Province[2022RC1230] ; Excellent youth funding of Hunan Provincial Education Department[22B0460] ; China Postdoctoral Science Foundation[2022M721542]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:001306623700014

IVYSPRING INT PUBL

Web of Science

1.Univ South China, Affiliated Nanhua Hosp, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Peoples R China
2.Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Peoples R China
3.Hunan Univ Med, Sch Pharmaceut Sci, Huaihua 418000, Peoples R China
4.Southern Univ Sci & Technol, Dept Chem, Xueyuan Blvd 1088, Shenzhen 518055, Peoples R China
5.Guangdong Pharmaceut Univ, Sch Chem & Chem Engn, Zhongshan 528458, Peoples R China
6.Guangdong Pharmaceut Univ, Guangdong Cosmet Engn & Technol Res Ctr, Zhongshan 528458, Peoples R China

Zhao, Cheng-Da,Cai, Wei,Chen, Wen-Jie,et al. Amide naphthotube as a novel supramolecular sequestration agent for tetracaine and decamethonium[J]. THERANOSTICS,2024,14(13).

Zhao, Cheng-Da.,Cai, Wei.,Chen, Wen-Jie.,Yao, Huan.,Wang, Song-Meng.,...&Yang, Liu-Pan.(2024).Amide naphthotube as a novel supramolecular sequestration agent for tetracaine and decamethonium.THERANOSTICS,14(13).

Zhao, Cheng-Da,et al."Amide naphthotube as a novel supramolecular sequestration agent for tetracaine and decamethonium".THERANOSTICS 14.13(2024).