Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms

Ketamine is an open channel blocker of ionotropic glutamatergic N-Methyl-D-Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects in patients with depression and treatment-resistant depression fostered novel effective treatments for mood disorders. This discovery not only provided new insight into the neurobiology of mood disorders but also uncovered fundamental synaptic plasticity mechanisms that underlie its treatment. In this review, we discuss key clinical aspects of ketamine's effect as a rapidly acting antidepressant, synaptic and circuit mechanisms underlying its action, as well as how these novel perspectives in clinical practice and synapse biology form a road map for future studies aimed at more effective treatments for neuropsychiatric disorders.

Automated summary

Ketamine is a channel blocker that targets NMDA receptors and has shown rapid antidepressant effects, providing a potential new treatment option for mood disorders. This discovery has not only given us a better understanding of the neurobiology of mood disorders, but also shed light on synaptic plasticity mechanisms for its treatment. In this review, we discuss the clinical aspects, synaptic and circuit mechanisms of ketamine, and how these insights can inform future studies for more effective treatments of neuropsychiatric disorders.