Oxime Induced Decarbamylation of Pyridostigmine Inhibited Acetylcholinesterase

摘要

It is generally believed that both carbamate and organophosphorus (OP) insecticides are toxic by virtue of their ability to inhibit acetylcholinesterase (AChE) enzyme. Pyridine-2-aldoxine (2-PAM) is used in conjunction with atropine for treatment of poisoning by OP insecticides. The efficacy of 2-PAM and other oxime derivatives against OP intoxication is due to their ability to reactivate the OP inhibited AChE. However, with soman, the inhibited AChE rapidly becomes resistant to oxime reactivation due to a phenomenon called aging. Thus, pretreatment by carbamates (e.g., pyridostigmine) followed by therapy with atropine and oxime required for significant protection against the class of rapidly aging OP's represented by soman, and the rationale for this regimen is based on the spontaneous regeneration of active AChE from a pool of carbamylated enzyme. This novel pretreatment/therapy regimen is clouded by a controversy concerning the use of oximes in the treatment of carbamate intoxication. Since pyridostigmine and an oxime may be used in rapid sequence in a poisonous chemical environment, it is important to elucidate the potential effects of oximes on the activity of carbamylated AChE in combination with known inhibitors. In this study we assessed the effects of two oximes 2-PAM and ( ( ( ( (4-aminocarbonyl)pyridino)methoxyl)methyl)-2-((hydroxyimino)methyl)- pyridinium dichloride)(HI-6) on carbamylation and decarbamylation of pyridostigmine treated blood AChE.