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BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1466351
Isoflurane-lipid emulsion injection as an anticonvulsant and neuroprotectant treatment for nerve agent exposure
Provisionally accepted- 1 Uniformed Services University of the Health Sciences, Bethesda, United States
- 2 The Ohio State University, Columbus, Ohio, United States
- 3 US Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, United States
We have shown that briefly inhaled isoflurane rapidly halts convulsions and protects the central nervous system (CNS) from organophosphate-induced neuronal loss when administered at 5% for 5 minutes, even as late as 1 hour after the nerve agent exposure. In the current study we investigated if an injectable form of isoflurane was as effective as inhaled isoflurane. We used a mixture of 10% isoflurane dissolved in an IV-compatible lipid-water emulsion for intravenous administration. Rats with an implanted jugular vein cannula were infused with 1000 microliters of the 10% isoflurane-lipid emulsion (ILE) mixture at a rate of 200 microliters per minute, which achieved full anesthesia lasting approximately 10 minutes. When administered 30 minutes after a highly lethal dose of the organophosphate insecticide paraoxon (POX), the short-duration administration halted convulsions permanently and prevented the great majority of neuronal loss as shown by Fluoro-Jade B staining (FJB). Our results indicate that injectable isoflurane is very effective for treating organophosphate poisoning, negating the need for vaporizer equipment and enabling intravenous therapy.
Keywords: Organophosphate Poisoning, Paraoxon, drug repurposing, Intravenous drug administration, convulsant antidote for nerve agents
Received: 17 Jul 2024; Accepted: 23 Sep 2024.
Copyright: © 2024 Krishnan, Moffett, Puthillathu, Johnson and Namboodiri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
John R. Moffett, Uniformed Services University of the Health Sciences, Bethesda, United States
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