Department of Neurology, University of Virginia, Charlottesville, VA 22908, United States of America.
Department of Neurology, University of Virginia, Charlottesville, VA 22908, United States of America; Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, United States of America; UVA Brain Institute, University of Virginia, Charlottesville, VA 22908, United States of America.
Epilepsy Behav. 2019 Dec;101(Pt B):106426. doi: 10.1016/j.yebeh.2019.07.027. Epub 2019 Aug 6.
This review summarizes the efforts of our laboratories to develop a mechanism-based therapy for the treatment of organophosphate (OP) nerve agent-induced seizures. Organophosphate poisoning can occur during warfare and terrorist attacks and in the civilian sphere because of intentional or unintentional poisoning. Persons exposed to OPs experience seizures. We developed animal models of OP poisoning and then evaluated the effects of OP on excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated glutamatergic neurotransmission in the hippocampus using patch-clamp electrophysiology. Organophosphate agents enhance glutamatergic transmission by enhancing neurotransmitter release. M1 muscarinic receptors mediate this effect, at least in part. Muscarinic receptors exert this action by inhibiting specific KCNQ2/3 potassium channels, which mediate the M-current. Flupirtine, a drug that open channels, is effective against OP-induced seizures. This article is part of the Special Issue"Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".
这篇综述总结了我们实验室为开发一种针对有机磷（OP）神经毒剂诱导的癫痫的基于机制的治疗方法所做的努力。有机磷中毒可能发生在战争和恐怖袭击期间，也可能因故意或无意中毒而发生在平民领域。接触过有机磷的人会出现癫痫发作。我们开发了有机磷中毒的动物模型，然后使用膜片钳电生理学评估了有机磷对海马中兴奋性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体介导的谷氨酸能神经传递的影响。有机磷剂通过增强神经递质释放来增强谷氨酸能传递。M1 毒蕈碱受体至少部分介导了这种作用。毒蕈碱受体通过抑制特定的 KCNQ2/3 钾通道发挥作用，该通道介导 M 电流。开放通道的药物氟吡汀对有机磷诱导的癫痫发作有效。本文是第 7 届伦敦-因斯布鲁克癫痫持续状态和急性发作研讨会特刊的一部分。
