Organophosphate (OP) induced seizures are commonly treated with anticholinergics, oximes and anticonvulsants. Inhibition of P-glycoprotein (PgP) has been shown to enhance the efficacy of nerve agent treatment in soman exposed rats. In the present study, the promising effects of the PgP inhibitor tariquidar were investigated in more detail in rats s.c. exposed to 150 μg/kg soman. Treatment with HI-6 and atropine sulfate (125 and 3 mg/kg i.m respectively) was administered 1 min after exposure. Diazepam (0.5 mg/kg i.m.) and/or tariquidar (7.5 mg/kg i.v.) were included either at 1 min or 40 min following onset of seizures.

Animals that received tariquidar, in addition to HI-6 and atropine, at 1 min, displayed a rapid normalization of EEG activity and cessation of seizure-associated behaviour. This improvement by addition of tariquidar was even more substantial in animals that also received diazepam, either immediately or delayed. Animals exhibiting lower intensity seizures displayed less severe neuropathology (neuronal loss, microglia activation and astrogliosis), primarily in the piriform cortex, and to a lesser extent amygdala and entorhinal cortex.

The present findings suggest that the interaction of tariquidar with atropine may be the decisive factor for enhanced treatment efficacy, given that atropine was previously found to be a PgP substrate. A more thorough understanding of the interactions of nerve agent antidotes, in particular the actions of central anticholinergics with benzodiazepines, could contribute to a future optimization of treatment combinations, particularly those aimed at later stage medical interventions.

有机磷酸酯（OP）诱发的癫痫发作通常用抗胆碱能药，肟和抗惊厥药治疗。业已证明，抑制P-糖蛋白（PgP）可以增强接触梭曼的大鼠中神经制剂的治疗效果。在本研究中，在暴露于150μg/ kg梭曼的大鼠皮下，对PgP抑制剂tariquidar的有希望的作用进行了更详细的研究。暴露后1分钟给予HI-6和硫酸阿托品（分别为125和3 mg / kg im）治疗。癫痫发作后1分钟或40分钟，包括地西p（0.5 mg / kg im）和/或塔利奎达（7.5 mg / kg iv）。

除HI-6和阿托品外，在1分钟时接受tariquidar的动物均表现出快速的EEG活性正常化和癫痫发作相关行为的停止。在还立即或延迟接受地西m的动物中，加入塔利奎达的改善作用更为明显。表现出较低强度癫痫发作的动物主要在梨状皮层中表现出较轻的神经病理学（神经元丢失，小胶质细胞活化和星形胶质变），在较小的程度上是杏仁核和内嗅皮层。

本研究结果表明，鉴于以前已发现阿托品是PgP底物，因此塔里基达与阿托品的相互作用可能是提高治疗效果的决定性因素。对神经毒剂解毒剂之间的相互作用，尤其是中枢抗胆碱能药与苯并二氮杂the的相互作用的更透彻的了解，可能有助于治疗组合的未来优化，尤其是针对后期医学干预的治疗组合。