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Molecular container mops up tricaine to reverse anaesthesia in fish

A lack of clinically available antidotes for general anaesthesia has prompted a team of researchers in China and Canada to explore the potential of a macrocyclic compound for halting anaesthesia in zebrafish. General anaesthetics put patients into reversible comas before surgery, but their effects can linger beyond their usefulness, resulting in neurotoxicity and cardiotoxicity, or in death, so if an equivalent molecule could be developed for humans it could save lives.

Cucurbit[n]urils are macrocycles that can inhibit the bioactivity of certain drugs by complexing and encapsulating them to neutralise their effects. Now, Ruibing Wang and co-workers at the University of Macao, China, and Queen’s University in Kingston, Canada, have shown that cucurbit[7]uril can encapsulate the anaesthetic tricaine within its lipophilic cavity. Tricaine acts as a general anaesthetic in cold-blooded animals and fish; in zebrafish it blocks ion channels within nerve membranes. Cucurbit[7]uril acts as a competitive receptor to remove tricaine from these channels and inhibit its anaesthetic properties. The resulting concentration gradient encourages any remaining tricaine to migrate away from the ion channel junction and into the plasma, to be snapped up by further host macrocycles.

To read the full article visit Chemistry World.

In vivo reversal of general anesthesia by cucurbit[7]uril with zebrafish models
Huanxian Chen, Judy Y. W. Chan, Shengke Li, Jessica J. Liu, Ian W. Wyman, Simon M. Y. Lee, Donal H. Macartney and Ruibing Wang
RSC Adv., 2015,5, 63745-63752
DOI: 10.1039/C5RA09406B

 

 

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