Glutamatergic transmission is widely implicated in neuropsychiatric disorders, and the discovery that ketamine elicits rapid-acting antidepressant effects by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) signaling has spurred a resurgence of interest in the field. This review explores agents in various stages of development for neuropsychiatric disorders that positively modulate AMPARs, both directly and indirectly. Despite promising preclinical research, few direct and indirect AMPAR positive modulators have progressed past early clinical development. Challenges such as low potency have created barriers to effective implementation. Nevertheless, the functional complexity of AMPARs sets them apart from other drug targets and allows for specificity in drug discovery. Additional effective treatments for neuropsychiatric disorders that work through positive AMPAR modulation may eventually be developed.

谷氨酸能传递广泛涉及神经精神疾病，氯胺酮通过调节 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPAR) 信号传导引起速效抗抑郁作用的发现激发了人们的兴趣在该领域。本综述探讨了直接和间接正向调节 AMPAR 的神经精神疾病的不同发展阶段的药物。尽管有前景的临床前研究，但很少有直接和间接的 AMPAR 正调节剂在早期临床开发之后取得进展。低效力等挑战为有效实施造成了障碍。然而，AMPAR 的功能复杂性使它们有别于其他药物靶标，并允许药物发现的特异性。