Glutamate-based antidepressants: 20 years on.
Phil Skolnick, Piotr Popik, Ramon Trullas
Trends in pharmacological sciences November 2009 DOI: 10.1016/j.tips.2009.09.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Commentary Peer reviewed |
|---|---|
| Key points | The authors argue that glutamate-based therapies may be an effective alternative to biogenic-amine-based antidepressants. They cite reports that the NR2B antagonist traxoprodil (CP 101 606) has antidepressant effects in patients unresponsive to a selective serotonin reuptake inhibitor, and that a single injection of the NMDA antagonist ketamine produces rapid and sustained antidepressant effects. They note that standard biogenic-amine drugs require two to four weeks for symptom improvement and relieve symptoms in only 60-65% of patients on a first course. |
Abstract
Depression is a chronic recurring illness that affects more than 120 million people worldwide. Drugs increasing the synaptic availability of serotonin and norepinephrine (biogenic amine-based agents) have been used to treat depression for more than 50 years. However, significant symptom improvement requires > or =2-4 weeks of treatment and a first course of therapy provides symptom relief to only 60-65% of patients. Roche and Evotec recently announced plans to develop N-methyl-D-aspartate (NMDA) receptor antagonists targeting the NR2B subtype for treatment-resistant depression. This announcement closely follows a report that another NR2B antagonist, traxoprodil (CP 101 606), has antidepressant effects in patients unresponsive to a serotonin selective reuptake inhibitor, as well as reports of rapid and sustained antidepressant effects following a single injection of the NMDA antagonist ketamine. Here we describe evidence that glutamate-based therapies might represent an effective alternative to biogenic-amine-based agents for depression and provide perspectives on the development of these agents.
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- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Ketamine and depression: a narrative review Drug Design, Development and Therapy August 1, 2019
- Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & Therapeutics July 1, 2019
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Cites 6
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression Biological Psychiatry July 9, 2009
- Family History of Alcohol Dependence and Initial Antidepressant Response to an NMDA Antagonist Biological Psychiatry November 8, 2008
- Lack of persistent effects of ketamine in rodent models of depression. Psychopharmacology June 2008
- Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biological Psychiatry February 15, 2008
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