Antagonism of propofol anesthesia by alkyl-fluorobenzene derivatives.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 Jul 2024
10 Jul 2024
Historique:
received:
08
01
2024
accepted:
03
07
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
10
7
2024
Statut:
epublish
Résumé
Despite their frequent use across many clinical settings, general anesthetics are medications with lethal side effects and no reversal agents. A fluorinated analogue of propofol has previously been shown to antagonize propofol anesthesia in tadpoles and zebrafish, but little further investigation of this class of molecules as anesthetic antagonists has been conducted. A 13-member library of alkyl-fluorobenzene derivatives was tested in an established behavioral model of anesthesia in zebrafish at 5 days post fertilization. These compounds were examined for their ability to antagonize propofol and two volatile anesthetics, as well as their interaction with the anesthetic-binding model protein apoferritin. Two compounds provided significant antagonism of propofol, and when combined, were synergistic, suggesting more than one antagonist sensitive target site. These compounds did not antagonize the volatile anesthetics, indicating some selectivity amongst general anesthetics. For the compounds with the most antagonistic potency, similarities in structure and binding to apoferritin may be suggestive of competitive antagonism; however, this was not supported by a Schild analysis. This is consistent with multiple targets contributing to general anesthesia, but whether these are physiologic antagonists or are antagonists at only some subset of the many anesthetic potential targets remains unclear, and will require additional investigation.
Identifiants
pubmed: 38987614
doi: 10.1038/s41598-024-66672-z
pii: 10.1038/s41598-024-66672-z
doi:
Substances chimiques
Propofol
YI7VU623SF
Fluorobenzenes
0
Apoferritins
9013-31-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15943Subventions
Organisme : Foundation for Anesthesia Education and Research
ID : MRTG
Organisme : Foundation for Anesthesia Education and Research
ID : MRTG
Organisme : Foundation for Anesthesia Education and Research
ID : MRTG
Organisme : Foundation for Anesthesia Education and Research
ID : MRTG
Organisme : Foundation for Anesthesia Education and Research
ID : MRTG
Organisme : NIGMS NIH HHS
ID : T32GM112596
Pays : United States
Informations de copyright
© 2024. The Author(s).
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