Ketamine and Memantine: Similar Mechanism of Action, But Not Antidepressant Activity

With research showing that ketamine, a noncompetitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, can be a rapidly acting antidepressant, there is clinical and research interest in whether other drugs with similar mechanisms of action, but without ketamine's adverse effects, possess this clinical activity. Memantine is an NMDA receptor antagonist, but does not appear to have rapid antidepressant effects. To explore the clinical discrepancy, researchers recently examined these two drugs' underlying functional differences in NMDA neurotransmission.

In several animal models, ketamine (but not memantine) produced effects indicative of antidepressant properties. In cultured hippocampal neurons, both memantine and ketamine an…