Conventional antidepressant medications, which act on monoaminergic systems, have significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. Recently, clinical findings demonstrate that ketamine, a dissociative anesthetic that blocks N-methyl-d-aspartate (NMDA) receptor channel activity, causes rapid (within hours) and long-lasting (7 to 10 days) antidepressant effects. Rapastinel is a novel glutamatergic compound that acts as an NMDAR postive allosteric modulator and produces rapid antidepressant actions in depressed patients and in preclinical rodent models. In addition, rapastinel has no ketamine-like side effect such as cognitive impairment and psychotomimetic symptoms. Despite recent negative clinical trials, it remains possible that rapastinel could prove effective as an alternative rapid agent with reduced side effects. In this review, we discuss the pharmacological profile of rapastinel and the molecular and cellular mechanisms underlying the rapid and sustained antidepressant actions of this novel agent.

作用于单胺能系统的常规抗抑郁药具有明显的局限性，包括数周至数月的时滞和较低的治疗效果。最近，临床发现表明氯胺酮是一种阻断N-甲基-d的解离性麻醉药-天冬氨酸（NMDA）受体通道活性，引起快速（数小时内）和持久（7至10天）的抗抑郁作用。雷帕斯汀是一种新型的谷氨酸能化合物，可作为NMDAR阳性变构调节剂，并在抑郁症患者和临床前啮齿动物模型中产生快速的抗抑郁作用。此外，雷帕替尼没有像氯胺酮一样的副作用，例如认知障碍和拟精神病症状。尽管最近出现了临床试验阴性，但雷帕替尼仍然有可能被证明是有效的替代快速药物，且副作用减少。在这篇综述中，我们讨论了雷帕替尼的药理作用以及这种新型药物快速和持续抗抑郁作用的分子和细胞机制。