Effective Countermeasure Against Poisoning by Organophosphorus Insecticides and Nerve Agents.
From: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, 21201, USA. ealbuque@umaryland.edu
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Aug 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 35
- Pages: 13220-5
- Medium: Print
- Language: English
- Citation (JAMA): Albuquerque Edson X, Pereira Edna F R, Aracava Yasco, et al. Effective Countermeasure Against Poisoning by Organophosphorus Insecticides and Nerve Agents.. Proc. Natl. Acad. Sci. U.S.A. Aug 2006;103:13220-5
Abstract
The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.
Mesh Headings (Keywords): Acetylcholinesterase, Animals, Atropine, Behavior, Animal, Brain, Chemical Warfare Agents, Cholinesterase Inhibitors, Dose-Response Relationship, Drug, Drug Therapy, Combination, Galantamine, Guinea Pigs, Insecticides, Lethal Dose 50, Neurons, Organophosphorus Compounds, Paraoxon, Poisoning, Pyridostigmine Bromide, Sarin, Sesquiterpenes, Soman, Time Factors
Check for Full Text / PubMed Unique Identifier (PMID): 16914529
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