首页> 美国卫生研究院文献>Springer Open Choice >Evaluation of the Anticonvulsant Effect of Brilliant Blue G a Selective P2X7 Receptor Antagonist in the iv PTZ- Maximal Electroshock- and 6 Hz-Induced Seizure Tests in Mice
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Evaluation of the Anticonvulsant Effect of Brilliant Blue G a Selective P2X7 Receptor Antagonist in the iv PTZ- Maximal Electroshock- and 6 Hz-Induced Seizure Tests in Mice

机译:选择性P2X7受体拮抗剂Brilliant Blue G在静脉内PTZ最大电击和6Hz诱发的癫痫发作试验中的抗惊厥作用评估

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摘要

Epilepsy is one of the most common neurological disorders which is diagnosed in around 65 million people worldwide. Clinically available antiepileptic drugs fail to control epileptic activity in about 30% of patients and they are merely symptomatic treatments and cannot cure or prevent epilepsy. There remains a need for searching new therapeutic strategies for epileptic disorders. The P2X7 receptor has been recently investigated as a new target in epilepsy treatment. Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant properties in some models of epilepsy. We aimed to investigate whether P2X7 receptor antagonist—brilliant blue G (BBG)—is able to change seizure threshold in three acute seizure models in mice, i.e., in the intravenous pentylenetetrazole seizure threshold, maximal electroshock seizure threshold and 6 Hz psychomotor seizure threshold tests. BBG was administered acutely (50–200 mg/kg, 30 min before the tests) and sub-chronically (25–100 mg/kg, once daily for seven consecutive days). Moreover, the chimney and grip strength tests were used to estimate the influence of BBG on the motor coordination and muscular strength in mice, respectively. Our results revealed only a week anticonvulsant potential of the studied P2X7 receptor antagonist because it showed anticonvulsant action only in the 6 Hz seizure test, both after acute and sub-chronic administration. BBG did not significantly influence seizure thresholds in the remaining tests. Motor coordination and muscular strength were not affected by the studied P2X7 receptor antagonist. In summary, BBG does not possess any remarkable anticonvulsant potential in acute seizure models in mice.
机译:癫痫病是最常见的神经系统疾病之一,全世界约有6500万人被诊断为癫痫病。临床上可用的抗癫痫药无法控制约30%的患者的癫痫活动,它们只是对症治疗,不能治愈或预防癫痫。仍然需要寻找新的癫痫病治疗策略。最近已经研究了P2X7受体作为癫痫治疗的新靶标。临床前研究表明,P2X7受体拮抗剂在某些癫痫模型中具有抗惊厥作用。我们旨在研究P2X7受体拮抗剂-亮蓝G(BBG)是否能够在小鼠的三种急性癫痫发作模型中更改癫痫发作阈值,即静脉内戊四唑癫痫发作阈值,最大电击癫痫发作阈值和6 Hz精神运动性癫痫发作阈值测试。 BBG急性给予(50-200 mg / kg,测试前30分钟),次慢性给予(25-100 mg / kg,连续7天每天一次)。此外,烟囱和抓地力测试分别用于评估BBG对小鼠运动协调和肌肉力量的影响。我们的结果显示,研究的P2X7受体拮抗剂仅一周可产生惊厥作用,因为它仅在急性和亚慢性给药后的6 Hz癫痫发作试验中才显示出惊厥作用。在其余测试中,BBG并未显着影响癫痫发作阈值。运动协调和肌肉力量不受研究的P2X7受体拮抗剂的影响。总之,BBG在小鼠的急性癫痫发作模型中不具有任何显着的抗惊厥潜能。

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