AMPA受体调节剂的抗疲劳促醒活性筛选

Screen of AMPA Receptor Modulators on Anti-fatigue and Wakefulness-promoting Effect

为寻找以α-氨基-3-羟基-5-甲基-4-异噁唑丙酸(α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid,AMPA)受体为靶点的新型抗疲劳促醒化合物,对以苯甲酰胺为母体,进行结构修饰后所合成的5个化合物(A2、A3、A4、D3、E2)进行活性筛选,通过小鼠负重游泳、睡眠剥夺坠水、戊巴比妥钠阈下睡眠试验,以睡眠潜伏期及维持、睡眠剥夺以及负重游泳时间,血清尿素氮及乳酸水平,肌糖原和肝糖原含量为指标,评价其抗疲劳促醒作用。结果表明,化合物A2可显著提高小鼠负重游泳时间、延长小鼠睡眠剥夺时间与睡眠潜伏期、降低其血清尿氮素及乳酸水平、对抗小鼠游泳后糖原变化,具有明显的抗疲劳促醒作用,优势显著,有进一步开发的价值。

Five synthetic compounds （A2, A3, A4, D3 and E2） were screened by experiments of mice burden swimming, sleep deprivation and pentobarbital induced hypnosis, for the exploration of novel anti-fatigue and wakefulness-promoting agents which target α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor. The evaluation indexes included the burden swimming time, maintain time of sleep deprivation, levels of blood urea nitrogen （BUN） and lactic acid （LD） in serum, contents of muscle glycogen and hepatic glycogen. According to the experiment results, compound A2 could extend the burden swimming time and maintain time of sleep deprivation. Meanwhile, it could also decrease the levels of BUN and LD in serum and increase the levels of muscle glycogen and hepatic glycogen, so it showed significant advantages on anti-fatigue and wakefulness-promoting effect. The further development of compound A2 could be considered.