Conventional antidepressant drugs elevate the availability of monoamine neurotransmitters. However, these pharmacological therapies have limited efficacy and a slow onset of action as main limitations. New glutamatergic drugs such as ketamine have shown promise as a rapid-acting antidepressant drugs although with adverse effects. The mechanism of action of ketamine is hypothesized to involve a dis-inhibition of cortical pyramidal neurons produced by an stimulation of AMPA receptors by glutamate. In this context, low-impact positive allosteric modulators of the AMPA receptors (a.k.a. ampakines) have been regarded as potential antidepressant drugs. Here, we have examined the behavioral, biochemical, and molecular effects of a low-impact ampakine, CX717. Our results show that CX717 has a rapid (30 min) but short-lasting (up to 24 h) antidepressant-like effect in the forced swim test. Intra-cortical infusion of CX717 increases the efflux of noradrenaline, dopamine, and serotonin, but not glutamate. However, systemic CX717 does not alter these neurotransmitters. CX717 also produced a rapid (up to 1 h) increase of brain-derived neurotrophic factor (BDNF) and a more sustained (up to 6 h) increase of p11. Overall, CX717 appears to possess a rapid but not sustained antidepressant action possibly caused by rapid increases of BDNF and p11.

传统的抗抑郁药物提高了单胺类神经递质的可用性。然而，这些药物疗法的主要限制是疗效有限和起效缓慢。新的谷氨酸能药物，如氯胺酮，已显示出作为速效抗抑郁药物的前景，尽管有副作用。据推测，氯胺酮的作用机制涉及对由谷氨酸刺激 AMPA 受体产生的皮质锥体神经元的去抑制作用。在这种情况下，AMPA 受体（又名安帕金斯）的低影响正变构调节剂被认为是潜在的抗抑郁药物。在这里，我们检查了低影响安帕金 CX717 的行为、生化和分子效应。我们的结果表明，CX717 在强迫游泳测试中具有快速（30 分钟）但持续时间短（长达 24 小时）的抗抑郁样作用。皮质内输注 CX717 会增加去甲肾上腺素、多巴胺和血清素的流出，但不会增加谷氨酸的流出。然而，全身性 CX717 不会改变这些神经递质。CX717 还产生了脑源性神经营养因子 (BDNF) 的快速（最多 1 小时）增加和 p11 更持续（最多 6 小时）的增加。总体而言，CX717 似乎具有快速但不持久的抗抑郁作用，这可能是由 BDNF 和 p11 的快速增加引起的。CX717 还产生了脑源性神经营养因子 (BDNF) 的快速（最多 1 小时）增加和 p11 更持续（最多 6 小时）的增加。总体而言，CX717 似乎具有快速但不持久的抗抑郁作用，这可能是由 BDNF 和 p11 的快速增加引起的。CX717 还产生了脑源性神经营养因子 (BDNF) 的快速（最多 1 小时）增加和 p11 更持续（最多 6 小时）的增加。总体而言，CX717 似乎具有快速但不持久的抗抑郁作用，这可能是由 BDNF 和 p11 的快速增加引起的。