During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with organophosphorus compounds. Their mechanism of action is reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus agents. Organophosphorus compounds (OPC) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OPC can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. The mechanism of OPC poisoning involves phosphorylation of the serine hydroxyl group at the active site of AChE leading to the inactivation of this essential enzyme, which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the central and peripheral nervous systems. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the standard pyridinium oximes (pralidoxime, trimedoxime, obidoxime, HI-6) and diazepam has been used for the treatment of organophosphate poisoning in humans. Despite enormous efforts devoted to synthesis and development of new pyridinium oximes as potential antidotes against poisoning with OPC, only four compounds have found their application in human medicine so far. However, they differ in their activity in poisoning with warfare nerve agents and pesticides and there is still no universal broad-spectrum oxime capable of protecting against all known OPC. In this article, we review data on structure-activity relationship of pyridinium oximes and discuss their pharmacological and toxicological significance.

中文翻译：

---

吡啶肟作为胆碱酯酶的活化剂。构效关系和功效在有机磷化合物中毒的治疗中。

在超过五十年的时间里，吡啶鎓肟已被开发为用于有机磷化合物中毒医学治疗的治疗剂。它们的作用机理是被有机磷试剂抑制的乙酰胆碱酯酶（AChE）的再活化。有机磷化合物（OPC）用作杀虫剂，并发展为战争神经毒剂，例如塔邦，梭曼，沙林，VX等。暴露于少量OPC可能会致命，并且死亡通常是由于respiratory肌和肋间肌麻痹，脑呼吸中枢凹陷，支气管痉挛和支气管分泌过多而导致的呼吸衰竭所致。OPC中毒的机制涉及AChE活性位点丝氨酸羟基的磷酸化，导致该必需酶失活，在神经传递中起重要作用。AChE抑制导致乙酰胆碱在胆碱能受体位点积聚，从而在整个中枢和周围神经系统中持续刺激胆碱能纤维。目前，抗毒蕈碱剂，例如阿托品，AChE活化剂如标准的吡啶鎓肟（普利多肟，三甲肟，obidoxime，HI-6）和地西epa的组合已用于治疗人类的有机磷酸盐中毒。尽管付出了巨大的努力来合成和开发新的吡啶鎓肟作为潜在的解毒剂，以防止OPC中毒，但迄今为止，只有四种化合物在人类医学中得到应用。然而，它们在使用战争神经毒剂和杀虫剂中毒方面的活性有所不同，并且仍然没有能够防御所有已知OPC的通用广谱肟。在本文中，我们综述了吡啶鎓肟的构效关系数据，并讨论了它们的药理和毒理学意义。