Format

Send to

Choose Destination
Drug Discov Today. 2019 Feb;24(2):606-615. doi: 10.1016/j.drudis.2018.11.007. Epub 2018 Nov 14.

A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.

Author information

1
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Connecticut Mental Health Center, New Haven, CT, USA. Electronic address: samuel.wilkinson@yale.edu.
2
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Connecticut Mental Health Center, New Haven, CT, USA.

Abstract

Mood disorders represent the largest cause of disability worldwide. The monoaminergic deficiency hypothesis, which has dominated the conceptual framework for researching the pathophysiology of mood disorders and the development of novel treatment strategies, cannot fully explain the underlying neurobiology of mood disorders. Mounting evidence collected over the past two decades suggests the amino acid neurotransmitter systems (glutamate and GABA) serve central roles in the pathophysiology of mood disorders. Here, we review progress in the development of compounds that act on these systems as well as their purported mechanisms of action. We include glutamate-targeting drugs, such as racemic ketamine, esketamine, lanicemine (AZD6765), traxoprodil (CP-101,606), EVT-101, rislenemdaz (CERC-301/MK-0657), AVP-786, AXS-05, rapastinel (formerly GLYX-13), apimostinel (NRX-1074/AGN-241660), AV-101, NRX-101, basimglurant (RO4917523), decoglurant (RG-1578/RO4995819), tulrampator (CX-1632/S-47445), and riluzole; and GABA-targeting agents, such as brexanolone (SAGE-547), ganaxolone, and SAGE-217.

PMID:
30447328
PMCID:
PMC6397075
[Available on 2020-02-01]
DOI:
10.1016/j.drudis.2018.11.007

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center