Acute organophosphorus compound (OP) poisoning induces symptoms of the cholinergic crises with the occurrence of severe epileptic seizures. Seizures are induced by hyperstimulation of the cholinergic system, but are enhanced by hyperactivation of the glutamatergic system. Overstimulation of muscarinic cholinergic receptors by the elevated acetylcholine causes glutamatergic hyperexcitation and an increased influx of Ca2+ into neurons through a type of ionotropic glutamate receptors, N‐methyl‐d‐aspartate (NMDA) receptors (NMDAR). These excitotoxic signaling processes generate reactive oxygen species, oxidative stress, and activation of the neuroinflammatory response, which can lead to recurrent epileptic seizures, neuronal cell death, and long‐term neurological damage. In this review, we illustrate the NMDAR structure, complexity of subunit composition, and the various receptor properties that change accordingly. Although NMDARs are in normal physiological conditions important for controlling synaptic plasticity and mediating learning and memory functions, we elaborate the detrimental role NMDARs play in neurotoxicity of OPs and focus on the central role NMDAR inhibition plays in suppressing neurotoxicity and modulating the inflammatory response. The limited efficacy of current medical therapies for OP poisoning concerning the development of pharmacoresistance and mitigating proinflammatory response highlights the importance of NMDAR inhibitors in preventing neurotoxic processes and points to new avenues for exploring therapeutics for OP poisoning.

中文翻译：

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N-甲基-d-天冬氨酸受体：结构、功能和在有机磷化合物中毒中的作用

急性有机磷化合物（OP）中毒会诱发胆碱能危象症状，并导致严重癫痫发作。癫痫发作是由胆碱能系统过度刺激引起的，但谷氨酸能系统过度激活会增强癫痫发作。乙酰胆碱升高对毒蕈碱胆碱能受体的过度刺激导致谷氨酸能过度兴奋和钙离子流入增加2+通过一种离子型谷氨酸受体进入神经元，氮-甲基-d‐天冬氨酸（NMDA）受体（NMDAR）。这些兴奋性毒性信号传导过程会产生活性氧、氧化应激和神经炎症反应的激活，从而导致癫痫反复发作、神经元细胞死亡和长期神经损伤。在这篇综述中，我们阐述了 NMDAR 结构、亚基组成的复杂性以及相应变化的各种受体特性。尽管 NMDAR 在正常生理条件下对于控制突触可塑性和介导学习和记忆功能非常重要，但我们详细阐述了 NMDAR 在 OP 神经毒性中所起的有害作用，并重点关注 NMDAR 抑制在抑制神经毒性和调节炎症反应中所起的核心作用。目前针对 OP 中毒的药物治疗在药物耐药性和减轻促炎反应方面的疗效有限，凸显了 NMDAR 抑制剂在预防神经毒性过程中的重要性，并为探索 OP 中毒治疗方法指明了新途径。