Abstract:
In this review, the current progress in the research and development of butyrylcholinesterase (BChE) reactivators is summarised and the advantages or disadvantages of these reactivators are critically discussed. Organophosphorus compounds such as nerve agents (sarin, tabun, VX) or pesticides (chlorpyrifos, diazinon) cause irreversible inhibition of acetylcholinesterase (AChE) and BChE in the human body. While AChE inhibition can be life threatening due to cholinergic overstimulation and crisis, selective BChE inhibition has presumably no adverse effects. Because BChE is mostly found in plasma, its activity is important for the scavenging of organophosphates before they can reach AChE in the central nervous system. Therefore, this enzyme in combination with its reactivator can be used as a pseudo-catalytic scavenger of organophosphates. Three structural types of BChE reactivators were found, i.e. bisquaternary salts, monoquaternary salts and uncharged compounds. Although the reviewed reactivators have certain limitations, the promising candidates for BChE reactivation were found in each structural group.
摘要:
在这次审查中,总结了丁酰胆碱酯酶(BChE)再激活剂的研究和开发的最新进展,并对这些再激活剂的优缺点进行了严格的讨论。有机磷化合物,如神经毒剂(沙林,tabun,VX)或杀虫剂(毒死蜱,二嗪农)引起人体内乙酰胆碱酯酶(AChE)和BChE的不可逆抑制。虽然由于胆碱能过度刺激和危象,AChE抑制可能危及生命,选择性BChE抑制可能没有副作用。因为BChE主要存在于血浆中,它的活性对于清除中枢神经系统中的AChE之前的有机磷酸盐很重要。因此,这种酶与它的再活化剂结合可以用作有机磷酸盐的假催化清除剂。发现了BChE再激活剂的三种结构类型,即双季铵盐,单季铵盐和不带电荷的化合物。虽然审查过的活化剂有一定的局限性,在每个结构组中发现了BChE再激活的有希望的候选者.