Institute for Medical Research and Occupational Health
Abstract
During the last five decades, five pyridinium oximes were found to be worthy of use as antidotes against nerve agents in humans: pralidoxime, in a form of chloride or PAM-2 Cl and mesylate or P2S (against sarin, cyclosarin and VX), trimedoxime or TMB-4 and obidoxime or LüH-6 (both against tabun, sarin and VX), HI-6 (against sarin, soman, cyclosarin and VX) and HLö-7 (against all the five nerve agents). In order to provide the auto-injector with the best and most potent acetylcholinesterase reactivator, the Defence Research and Development Canada (DRDC) received in the 1990s a core funding from the federal government’s CBRN research and Technology Initiative (CRTI). Its ultimate result should be three products: (1) 3-in-1 auto-injector (atropine, HI-6 dimethanesulphonate and avizafone, as anticonvulsant), (2) 2-in-1 auto-injector (atropine and HI-6 dimethanesulphonate) and (3) HI-6 dimethanesulphonate in a vial for administration by the medically trained personnel. Previous experimental and clinical experience suggests that, among the oximes mentioned, only trimedoxime and obidoxime can be used for acetylcholinesterase reactivation and antidotal protection against most of the organophosphorus insecticides. The search for an “omnipotent” oxime, effective in reactivation of AChE inhibited with both nerve agents and organophosphorus insecticides, is still ongoing.Tijekom proteklih pet desetljeća, za pet piridinijevih oksima ustanovljeno je da zavređuju da budu upotrijebljeni kod ljudi kao antidoti protiv živanih bojnih otrova: pralidoksim, u obliku klorida, PAM-2 Cl ili mesilat, P2S (protiv sarina, ciklosarina i VX-otrova), trimedoksim ili TMB-4 i obidoksim ili LüH-6 (oba protiv tabuna, sarin i VX-otrova), HI-6 (protiv sarina, somana, ciklosarina i VX-otrova) i HLö-7 (protiv svih pet živanih bojnih otrova). Radi osiguranja autoinjektora s najboljim i najpotentnijim reaktivatorom acetilkolinesteraze, Kanadska uprava za obrambena istraživanja i razvoj (DRDC) primila je tijekom 1990-ih godina osnovnu financijsku potporu od Istraživačke i tehnološke inicijative u oblasti kemijske, biološke, radiološke i nuklearne zaštite (CRTI) Vlade Kanade. DRDC će primati financijsku i znanstvenu pomoć suradnjom šest zemalja (izmeu Kanade, Njemake, Nizozemske, Norveške, Švedske i Velike Britanije). Njezin bi krajnji rezultat trebala biti tri proizvoda: (1) “3-u-1” autoinjektor (atropin, HI-6 dimetansulfonat i avizafon, kao antikonvulzant), (2) “2-u-1” autoinjektor (atropin i HI-6 dimetansulfonat) i (3) HI-6 dimetansulfonat u bočici za primjenu od medicinski obrazovanog osoblja. Prethodna eksperimentalna i klinika iskustva sugeriraju da, među spomenutim oksimima, jedino trimedoksim i obidoksim, koji su relativno toksini per se, mogu osigurati reaktivaciju acetilkolinesteraze i antidotsku zaštitu protiv većine organofosfornih insekticida. Potraga za “omnipotentnim” oksimom, djelotvornim i protiv svih živanih bojnih otrova i protiv svih organofosfornih insekticida, još je u toku
