Search

This paper describes an in vitro study of three potential acetylcholinesterase (AChE; EC 3.1.1.7) reactivators derived from a monoquaternary reactivator pralidoxime. Compounds used were pyridinium-2-aldoxime-4- carbamoyl-N-methyl iodide (TO231), pyridinium-2-aldoxime-4-ethoxycarbonyl-N-methyl iodide (TO237), and pyridinium-2-aldoxime-5-ethoxycarbonyl-N-methyl iodide (TO238). Pralidoxime and obidoxime were used for comparison. Nerve agent cyclosarin and pesticide chlorpyrifos were used as organophosphorus cholinesterase inhibitors. The source of AChE was rat brain homogenate. None of the tested oximes was able to reactivate cyclosarin-inhibited AChE (at 1.0 mmol L-1 oxime concentration). In case of chlorpyrifos, TO231 was the most potent AChE reactivator with an 82 % reactivation at 1.0 mmol L-1 oxime concentration. This reactivating potency equals that of pralidoxime and obidoxime. TO238 was less effective, and TO237 did not reactivate chlorpyrifos-inhibited AChE at all. None of the tested AChE reactivators, reference compounds included, could be considered universal for both chlorpyrifos- and cyclosarin-inhibited AChE., U ovome in vitro istraživanju testiran je reaktivacijski potencijal triju reaktivatora acetilkolinesteraze (AChE; EC 3.1.1.7) dobivenih iz monokvaternog reaktivatora pralidoksima. Testirani su sljedeći spojevi: 4-karbamoil-2-aldoksim-1-metilpiridinijev jodid (TO231), 4-etoksikarbonil-2-aldoksim-1-metilpiridinijev jodid (TO237) te 5-etoksikarbonil-2-aldoksim-1-metilpiridinijev jodid (TO238). Za usporedbu su uzeti pralidoksim i obidoksim. Kao inhibitori kolinesteraze rabljeni su živćani otrov ciklosarin i pesticid klorpirifos. Izvor acetilkolinesteraze bio je homogenat mozga štakora. Nijedan od testiranih oksima nije uspio reaktivirati acetilkolinesterazu inhibiranu ciklosarinom pri koncentraciji oksima od 1.0 mmol L-1. Kod inhibicije klorpirifosom TO231 pokazao se najsnažnijim reaktivatorom acetilkolinesteraze s reaktivacijom od 82 % pri koncentraciji oksima od 1.0 mmol L-1. Ovaj reaktivacijski potencijal jednak je onomu pralidoksima i obidoksima. Slabiju je djelotvornost iskazao TO238, a TO237 nije uspio reaktivirati acetilkolinesterazu inhibiranu klorpirifosom. Stoga nijedan od testiranih spojeva (uključujući i referentne oksime) ne može služiti kao univerzalni reaktivator acetilkolinesteraze inhibirane klorpirifosom i ciklosarinom.