The role of NMDARs in the anesthetic and antidepressant effects of ketamine.

Ketamine, a dissociative anesthetic and PCP analog, produces rapid loss of consciousness at anesthetic doses and rapid, lasting antidepressant effects at subanesthetic doses. This review describes ketamine's metabolism and recent advances in understanding how NMDAR inhibition mediates both effects. The roles of NMDARs in anesthesia are well studied, but their involvement in antidepressant actions is complex and debated. The authors also explore possible functions of NMDAR subunits and discuss future directions for ketamine-based drugs.

Study at a glance

Abstract

As a phencyclidine (PCP) analog, ketamine can generate rapid-onset and substantial anesthetic effects. Contrary to traditional anesthetics, ketamine is a dissociative anesthetic and can induce loss of consciousness in patients. Recently, the subanaesthetic dose of ketamine was found to produce rapid-onset and lasting antidepressant effects. However, how different concentrations of ketamine can induce diverse actions remains unclear. Furthermore, the molecular mechanisms underlying the NMDAR-mediated anesthetic and antidepressant effects of ketamine are not fully understood. In this review, we have introduced ketamine and its metabolism, summarized recent advances in the molecular mechanisms underlying NMDAR inhibition in the anesthetic and antidepressant effects of ketamine, explored the possible functions of NMDAR subunits in the effects of ketamine, and discussed the future directions of ketamine-based anesthetic and antidepressant drugs. Both the anesthetic and antidepressant effects of ketamine were thought to be mediated by N-methyl-D-aspartate receptor (NMDAR) inhibition. The roles of NMDARs have been extensively studied in the anaesthetic effects of ketamine. However, the roles of NMDARs in antidepressant effects of ketamine are complicated and controversial.