Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents Export

@article{Albuquerque:2006, 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{\^a}€™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.}, annote = {Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents}, author = {Albuquerque, E. X. and Pereira, E. F. R. and Aracava, Y. and Fawcett, W. P. and Oliveira, M. and Randall, W. R. and Hamilton, T. A. and Kan, R. K. and Jr and Adler, M.}, citeulike-article-id = {1331437}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0605370103}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {acetylcholinesterase, nerve\_agents, neuromuscular\_junctions}, number = {35}, pages = {13220--5}, posted-at = {2007-05-25 14:23:18}, priority = {0}, title = {Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents}, url = {http://dx.doi.org/10.1073/pnas.0605370103}, volume = {103}, year = {2006} }

TY - JOUR ID - Albuquerque:2006 L3 - citeulike-article-id:1331437 N2 - 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{\^a}€™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. IS - 35 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 5 TI - Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents VL - 103 SP - 13220 KW - acetylcholinesterase KW - nerve_agents KW - neuromuscular_junctions AU - Albuquerque, EX AU - Pereira, EFR AU - Aracava, Y AU - Fawcett, WP AU - Oliveira, M AU - Randall, WR AU - Hamilton, TA AU - Kan, RK AU - Jr AU - Adler, M PY - 2006/// UR - http://dx.doi.org/10.1073/pnas.0605370103 ER -