title: Molecular and cellular actions of galantamine: clinical implications for treatment of organophosphorus poisoning.
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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Edna F R
authors.initials: EF
authors.lastname: Pereira
authors.forename: Yasco
authors.initials: Y
authors.lastname: Aracava
authors.forename: Manickavasagom
authors.initials: M
authors.lastname: Alkondon
authors.forename: Miriam
authors.initials: M
authors.lastname: Akkerman
authors.forename: Istvan
authors.initials: I
authors.lastname: Merchenthaler
authors.forename: Edson X
authors.initials: EX
authors.lastname: Albuquerque
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002619:Chemical Warfare Agents / Q000633:toxicity; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002801:Cholinesterase Reactivators / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D005702:Galantamine / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D009924:Organ Culture Techniques; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors*; D012524:Sarin / Q000037:antagonists & inhibitors / Q000633:toxicity; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D009943:Organophosphorus Compounds; D005702:Galantamine; D001285:Atropine; D012999:Soman; D012524:Sarin; D000110:Acetylcholinesterase
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