Targeting glutamate signalling in depression: Progress and prospects

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309 Scopus citations

Abstract

Major depressive disorder (MDD) is severely disabling, and current treatments have limited efficacy. The glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine was recently repurposed as a rapidly acting antidepressant, catalysing the vigorous investigation of glutamate-signalling modulators as novel therapeutic agents for depressive disorders. In this Review, we discuss the progress made in the development of such modulators for the treatment of depression, and examine recent preclinical and translational studies that have investigated the mechanisms of action of glutamate-targeting antidepressants. Fundamental questions remain regarding the future prospects of this line of drug development, including questions concerning safety and tolerability, efficacy, dose-response relationships and therapeutic mechanisms.

Original languageEnglish
Pages (from-to)472-486
Number of pages15
JournalNature Reviews Drug Discovery
Volume16
Issue number7
DOIs
StatePublished - 1 Jul 2017
Externally publishedYes

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