Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function.

ABSTRACT: Efforts to develop efficacious antidepressant agents with novel mechanisms have been largely unsuccessful since the 1950's until the discovery of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist that produces rapid and sustained antidepressant actions even in treatment-resistant patients. This finding has ushered in a new era for the development of novel rapid-acting antidepressants that act at the NMDA receptor complex, but without dissociative and psychotomimetic side effects of ketamine. Here, we review the current state of rapid-acting antidepressant drug development, including NMDA channel blockers, glycine site agents, and allosteric modulators, as well as ketamine stereoisomers and metabolites. In addition, we focus on the neurobiological mechanisms underlying the action

SUBMITTER: Duman RS 

PROVIDER: S-EPMC6754322 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature