Abstract |
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 x 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 x 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 x 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 x LD50 soman. The results presented herein corroborate that galantamine is an effective antidote against OP poisoning.
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Authors | Edna F R Pereira, Yasco Aracava, Manickavasagom Alkondon, Miriam Akkerman, Istvan Merchenthaler, Edson X Albuquerque |
Journal | Journal of molecular neuroscience : MN
(J Mol Neurosci)
Vol. 40
Issue 1-2
Pg. 196-203
(Jan 2010)
ISSN: 1559-1166 [Electronic] United States |
PMID | 19690988
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Chemical Warfare Agents
- Cholinesterase Inhibitors
- Cholinesterase Reactivators
- Muscarinic Antagonists
- Organophosphorus Compounds
- Galantamine
- Atropine
- Soman
- Sarin
- Acetylcholinesterase
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Topics |
- Acetylcholinesterase
(drug effects, metabolism)
- Animals
- Atropine
(pharmacology)
- Brain
(drug effects, metabolism, pathology)
- Chemical Warfare Agents
(toxicity)
- Cholinergic Fibers
(drug effects, metabolism, pathology)
- Cholinesterase Inhibitors
(pharmacology, therapeutic use)
- Cholinesterase Reactivators
(pharmacology, therapeutic use)
- Drug Interactions
(physiology)
- Female
- Galantamine
(pharmacology, therapeutic use)
- Guinea Pigs
- Lethal Dose 50
- Male
- Muscarinic Antagonists
(pharmacology)
- Nerve Degeneration
(chemically induced, drug therapy, prevention & control)
- Organ Culture Techniques
- Organophosphate Poisoning
- Organophosphorus Compounds
(antagonists & inhibitors)
- Sarin
(antagonists & inhibitors, toxicity)
- Soman
(antagonists & inhibitors, toxicity)
- Treatment Outcome
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