New synthesized oximes active in nerve agents’ hazards
Journal Title: Revista de Medicină Militară - Year 2017, Vol 0, Issue 2
Abstract
Object: The aim of the study is to select the most active new imidazolium-quinuclidinum-oxime, from some similar chemical compounds synthesized in our chemistry department, with sufficient efficacy to decrease the acute toxicity of neurotoxic organophosphates known as nerve agents. Method: The experimental study consist in vivo testing the antidotal efficacy of obidoxime and of selected imidazolium oximes synthesized in our chemistry department. Each oxime was included, by equimolar replacing the obidoxime, in an antidotal formula, which also contains atropine. The above mentioned formula containing atropine and obidoxime was used as reference. The protective ratio, defined as the ratio between the lethal median dose of the poisoned and treated study group and the median lethal dose (LD50) of the poisoned and untreated study groups was one of the used parameters in order to select a new active chemical structure in counteracting the neurotoxic organophosphorus compounds acute toxicity. Another studied parameter was the erythrocyte acetylcholinesterase value measured in whole blood 24 hours after exposure. Results: The protective ratio against an organophosphorus compound were the follow: obidoxime chloride: 2; 1,3-dimethyl-2-hydroxyethyl-imidazolyliodide: 1,75;3-oxime-[3-(2-hidroxyimino-methyl-1-imidazolyl-)-2oxapropyl]quinuclidin-dichl-oride: 2,5; 1-methyl-quinuclidin-3-iodide: 1,5. The erythrocyte acetycholinesterase main values were the following: the unpoisoned and untreated study group:3,45 ±0,13mmol/dl; the poisoned and untreated study group: 0,89 ±0,09 mmol/dl; the poisoned and 3-oxime-[3-(2-hidroxyimino-methyl-1-imidazolyl-)-2oxapropyl]quinuclidindichloride treated study group:2,89 ±0,11 mmol/dl; the poisoned and obidoxime treated study group: 2,53±0,15 mmol/dl. Conclusions: 3-oxime-[3-(2-hidroxyimino-methyl-1-imidazolyl-)-2oxapropyl] quinuclidindichloride synthesized in our chemistry department, has shown a better protective ratio and a more prolonged surviving time than the reference (obidoxime). It has shown the best AChE reactivation of all the synthetized compounds. This compound can be a cheap and good option for replacing obidoxime in the antidotal formula active in nerve agent exposure
Authors and Affiliations
Mihail Tudosie, Bogdan Patrinich, Andreea Negrea, Cristina Secara
Keywords
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