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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Acetylcholinesterase / drug effects
-
Acetylcholinesterase / metabolism
-
Animals
-
Atropine / pharmacology
-
Brain / drug effects
-
Brain / metabolism
-
Brain / pathology
-
Chemical Warfare Agents / toxicity
-
Cholinergic Fibers / drug effects
-
Cholinergic Fibers / metabolism
-
Cholinergic Fibers / pathology
-
Cholinesterase Inhibitors / pharmacology*
-
Cholinesterase Inhibitors / therapeutic use
-
Cholinesterase Reactivators / pharmacology*
-
Cholinesterase Reactivators / therapeutic use
-
Drug Interactions / physiology
-
Female
-
Galantamine / pharmacology*
-
Galantamine / therapeutic use
-
Guinea Pigs
-
Lethal Dose 50
-
Male
-
Muscarinic Antagonists / pharmacology
-
Nerve Degeneration / chemically induced
-
Nerve Degeneration / drug therapy
-
Nerve Degeneration / prevention & control
-
Organ Culture Techniques
-
Organophosphate Poisoning*
-
Organophosphorus Compounds / antagonists & inhibitors*
-
Sarin / antagonists & inhibitors
-
Sarin / toxicity
-
Soman / antagonists & inhibitors
-
Soman / toxicity
-
Treatment Outcome
Substances
-
Chemical Warfare Agents
-
Cholinesterase Inhibitors
-
Cholinesterase Reactivators
-
Muscarinic Antagonists
-
Organophosphorus Compounds
-
Galantamine
-
Atropine
-
Soman
-
Sarin
-
Acetylcholinesterase