Nerve agents inhibit acetylcholinesterase (AChE), leading to a build-up of acetylcholine (ACh) and overstimulation at cholinergic synapses. Current post-exposure nerve agent treatment includes atropine to treat overstimulation at muscarinic synapses, a benzodiazepine anti-convulsant, and an oxime to restore the function of AChE. Aside from the oxime, the components do not act directly to reduce the overstimulation at nicotinic synapses. The false transmitters acetylmonoethylcholine (AMECh) and acetyldiethylcholine (ADECh) are analogs of ACh, synthesised similarly at synapses. AMECh and ADECh are partial agonists, with reduced activity compared to ACh, so it was hypothesised the false transmitters could reduce overstimulation. Synthetic routes to AMECh and ADECh, and their precursors, monoethylcholine (MECh) and diethylcholine (DECh), were devised, allowing them to be produced easily on a laboratory-scale. The mechanism of action of the false transmitters was investigated in vitro. AMECh acted as a partial agonist at human muscarinic (M1 and M3) and muscle-type nicotinic receptors, and ADECh was a partial agonist only at certain muscarinic subtypes. Their precursors acted as antagonists at muscle-type nicotinic, but not muscarinic receptors. Administration of MECh and DECh improved neuromuscular function in the soman-exposed guinea-pig hemi-diaphragm preparation. False transmitters may therefore help reduce nerve agent induced overstimulation at cholinergic synapses.

中文翻译：

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假递质作为神经毒剂中毒治疗的评估

神经毒剂抑制乙酰胆碱酯酶 (AChE)，导致乙酰胆碱 (ACh) 的积聚和胆碱能突触的过度刺激。目前的暴露后神经毒剂治疗包括治疗毒蕈碱突触过度刺激的阿托品、苯二氮卓类抗惊厥药和恢复 AChE 功能的肟。除了肟，这些成分不会直接减少烟碱突触的过度刺激。假递质乙酰单乙基胆碱 (AMECh) 和乙酰二乙基胆碱 (ADECh) 是 ACh 的类似物，在突触处合成类似。AMECh 和 ADECh 是部分激动剂，与 ACh 相比活性降低，因此假设假递质可以减少过度刺激。设计了 AMECh 和 ADECh 及其前体单乙基胆碱 (MECh) 和二乙基胆碱 (DECh) 的合成路线，允许它们在实验室规模上轻松生产。体外研究了假递质的作用机制。AMECh 对人类毒蕈碱（M1 和 M3）和肌肉型烟碱受体起部分激动剂作用，而 ADECh 仅对某些毒蕈碱亚型起部分激动剂作用。它们的前体作为肌肉型烟碱的拮抗剂，而不是毒蕈碱受体。MECh 和 DECh 的给药改善了暴露于梭曼的豚鼠半横隔膜制剂中的神经肌肉功能。因此，假递质可能有助于减少神经毒剂引起的胆碱能突触过度刺激。AMECh 对人类毒蕈碱（M1 和 M3）和肌肉型烟碱受体起部分激动剂作用，而 ADECh 仅对某些毒蕈碱亚型起部分激动剂作用。它们的前体作为肌肉型烟碱的拮抗剂，而不是毒蕈碱受体。MECh 和 DECh 的给药改善了暴露于梭曼的豚鼠半横隔膜制剂中的神经肌肉功能。因此，假递质可能有助于减少神经毒剂引起的胆碱能突触过度刺激。AMECh 对人类毒蕈碱（M1 和 M3）和肌肉型烟碱受体起部分激动剂作用，而 ADECh 仅对某些毒蕈碱亚型起部分激动剂作用。它们的前体作为肌肉型烟碱的拮抗剂，而不是毒蕈碱受体。MECh 和 DECh 的给药改善了暴露于梭曼的豚鼠半横隔膜制剂中的神经肌肉功能。因此，假递质可能有助于减少神经毒剂引起的胆碱能突触过度刺激。