Combination of acetylcholinesterase inhibitors and NMDA receptor antagonists increases survival rate in soman-poisoned mice
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
- Keywords
- HI-6, Soman, atropine, donepezil, huperzine A, memantine, mice, procyclidine,
- MeSH
- Acetylcholinesterase metabolism MeSH
- Antidotes therapeutic use MeSH
- Atropine therapeutic use pharmacology MeSH
- Cholinesterase Inhibitors toxicity MeSH
- Poisons * MeSH
- Memantine therapeutic use MeSH
- Survival Rate MeSH
- Mice MeSH
- Oximes therapeutic use pharmacology MeSH
- Procyclidine pharmacology MeSH
- Pyridinium Compounds pharmacology MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
- Soman * toxicity MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Antidotes MeSH
- Atropine MeSH
- Cholinesterase Inhibitors MeSH
- huperzine A MeSH Browser
- Poisons * MeSH
- Memantine MeSH
- Oximes MeSH
- Procyclidine MeSH
- Pyridinium Compounds MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
- Soman * MeSH
Organophosphorus nerve agents pose a global threat to both military personnel and civilian population, because of their high acute toxicity and insufficient medical countermeasures. Commonly used drugs could ameliorate the intoxication and overall medical outcomes. In this study, we tested the drugs able to alleviate the symptoms of Alzheimer's disease (donepezil, huperzine A, memantine) or Parkinson's disease (procyclidine). They were administered to mice before soman intoxication in terms of their: i) protection potential against soman toxicity and ii) influence on post-exposure therapy consisting of atropine and asoxime (also known as oxime HI-6). Their pretreatment effect was not significant, when administered alone, but in combination (acetylcholinesterase inhibitor such as denepezil or huperzine A with NMDA antagonist such as memantine or procyclidine) they lowered the soman toxicity more than twice. These combinations also positively influenced the efficacy of post-exposure treatment in a similar fashion; the combinations increased the therapeutic effectiveness of antidotal treatment. In conclusion, the most effective combination - huperzine A and procyclidine - lowered the toxicity three times and improved the post-exposure therapy efficacy more than six times. These results are unprecedented in the published literature.
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