Molecular and Cellular Actions of Galantamine: Clinical Implications for Treatment of Organophosphorus Poisoning
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- Pereira, E.F.R., Aracava, Y., Alkondon, M. et al. J Mol Neurosci (2010) 40: 196. doi:10.1007/s12031-009-9234-3
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There have been continued efforts to develop effective antidotal therapies against poisoning with organophosphorus (OP) compounds, including nerve agents and pesticides. We reported recently that galantamine, a drug used to treat Alzheimer’s disease, administered before (up to 3 h) or soon after (up to 5 min) an exposure of guinea pigs to 1.5–2 × LD50 soman or sarin effectively counteracted the acute toxicity and lethality of the nerve agents provided that the animals were also post-treated with atropine. Here, we demonstrate that administered to guinea pigs at 30 min before or up to 15 min after an acute challenge with 1 × LD50 soman, galantamine (8 mg/kg, intramuscular) alone is sufficient to counteract the lethality and acute toxicity of the nerve agent. Evidence is also provided that 100% survival can be attained when the association of appropriate doses of galantamine and atropine is administered 30–45 min after the challenge of the guinea pigs with 1 × LD50 soman. Galantamine counteracts the neurodegeneration and the changes in the nicotinic cholinergic system that result from an acute exposure of guinea pigs to 1 × LD50 soman. The results presented herein corroborate that galantamine is an effective antidote against OP poisoning.