Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents
| Autor: | Robert K. Kan, Edna F. R. Pereira, William P. Fawcett, Yasco Aracava, William R. Randall, Edson X. Albuquerque, Tracey A. Hamilton, Michael Adler, Maristela Oliveira, James A. Romano |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Atropine
Insecticides Sarin Time Factors Guinea Pigs Soman Pharmacology Organophosphate poisoning Paraoxon Lethal Dose 50 chemistry.chemical_compound Alkaloids Organophosphate Poisoning Organophosphorus Compounds medicine Galantamine Animals Chemical Warfare Agents Nerve agent Tabun Neurons Multidisciplinary Behavior Animal Dose-Response Relationship Drug Poisoning Brain medicine.disease Acetylcholinesterase chemistry Commentary Drug Therapy Combination Cholinesterase Inhibitors Sesquiterpenes Pyridostigmine Bromide medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:13220-13225 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0605370103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|