Abstract：
Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.
摘要：
重度抑郁症（MDD）是一种慢性复发性精神疾病。传统的抗抑郁药通常需要连续给药数周才能发挥临床上显著的治疗效果。而约三分之二的患者容易症状复发或在抗抑郁治疗中完全无效。最近成功的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂氯胺酮作为一种快速作用的抗抑郁药，推动了对抗抑郁药作用机制的广泛研究。尤其是它在突触靶标中的作用。研究表明，氯胺酮的抗抑郁作用机制不仅限于突触后NMDA受体或GABA中间神经元的拮抗作用。氯胺酮通过影响α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体产生强大而快速的抗抑郁作用，腺苷A1受体，和L型钙通道,在突触中。更有趣的是，在抑郁小鼠模型和临床研究中,5-HT2A受体激动剂psilocybin具有快速抗抑郁作用的潜力.本文重点介绍了新兴的快速作用抗抑郁药物如氯胺酮和致幻剂的新药理靶点研究（例如，psilocybin）并简要讨论了抗抑郁药新靶点的可能策略，以期阐明未来抗抑郁药研究的方向。
