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
Open accessAbstract
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.
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References 47 · Cited by 173
Research works printed but not linked: 1
- [46]Paterson B (2015) A randomized, double-blind, placebo-controlled, sequential parallel study of CERC-301 in the adjunctive treatment of subjects with severe depression and recent active suicidal ideation despite antidepressant treatment. Poster/abstract presented at National Network of Depression Centers, Annual Conference, Annual Conference, Ann Arbor, Michigan; Nov 5–6, 2015.
- Authors
- Wilkinson, S. T., & Sanacora, G.
- Affiliations
- Yale University (US)
- Corresponding author
- Wilkinson, Samuel T.
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 24
- Issue
- 2
- Pages
- 606-615
- ISSN
- 1359-6446 (ISSN-L)
- PMC
- PMC6397075
- OpenAlex
- W2900628218
- Cited by
- 173
- References
- 47
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 21 · 2023: 20 · 2022: 28 · 2021: 32 · 2020: 28 · 2019: 17 · 2018: 1
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Agency for Healthcare Research and Quality (K12HS023000)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- antidepressants, mood disorders, ketamine, esketamine, risperidone, riluzole, brexanolone, ganaxolone, rapid-acting antidepressants, drug development pipeline
- MeSH terms
- Animals, Antidepressive Agents, gamma-Aminobutyric Acid, Humans, Glutamic Acid, Mood Disorders
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