A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pre-treatment of soman-poisoned mice
Language English Country Great Britain, England Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antidotes administration & dosage pharmacology MeSH
- Atropine administration & dosage pharmacology MeSH
- Chemical Warfare Agents poisoning MeSH
- Cholinesterase Inhibitors administration & dosage pharmacology MeSH
- Isoquinolines administration & dosage pharmacology MeSH
- Drug Therapy, Combination MeSH
- Lethal Dose 50 MeSH
- Mice MeSH
- Oximes administration & dosage pharmacology MeSH
- Pyridinium Compounds administration & dosage pharmacology MeSH
- Pyridostigmine Bromide administration & dosage pharmacology MeSH
- Cholinesterase Reactivators administration & dosage pharmacology MeSH
- Soman administration & dosage poisoning MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- 1,10-bis(pyridinium)decane MeSH Browser
- 1,8-bis(4-tert-butylpyridinium)oct-1,8-diyl MeSH Browser
- 1,8-bis(isoquinolinium)-oct-1,8-diyl MeSH Browser
- Antidotes MeSH
- asoxime chloride MeSH Browser
- Atropine MeSH
- Chemical Warfare Agents MeSH
- Cholinesterase Inhibitors MeSH
- Isoquinolines MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Pyridostigmine Bromide MeSH
- Cholinesterase Reactivators MeSH
- Soman MeSH
The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50) value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre-treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising.
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