Article

Glutamate-based antidepressants: 20 years on.

Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
Trends in Pharmacological Sciences (Impact Factor: 9.99). 11/2009; 30(11):563-9. DOI: 10.1016/j.tips.2009.09.002
Source: PubMed

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.

Download full-text

Full-text

Available from: Ramon Trullas, Jun 20, 2015
0 Followers
 · 
174 Views
  • Source
    Dataset: 75
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major depression is a prevalent and debilitating disorder and a substantial proportion of patients fail to reach remission following standard antidepressant pharmacological treatment. Limited efficacy with currently available antidepressant drugs highlights the need to develop more effective medications for treatment resistant patients and emphasizes the importance of developing better preclinical models that focus on treatment resistant populations. This review discusses methods to adapt and refine rodent behavioral models that are predictive of antidepressant efficacy to identify populations that show reduced responsiveness or are resistant to traditional antidepressants. Methods include separating antidepressant responders from non-responders, administering treatments that render animals resistant to traditional pharmacological treatments, and identifying genetic models that show antidepressant resistance. This review also examines pharmacological and non-pharmacological treatments regimes that have been effective in refractory patients and how some of these approaches have been used to validate animal models of treatment-resistant depression. The goals in developing rodent models of treatment- resistant depression are to understand the neurobiological mechanisms involved in antidepressant resistance and to develop valid models to test novel therapies that would be effective in patients that do not respond to traditional monoaminergic antidepressants. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 11/2014; 753. DOI:10.1016/j.ejphar.2014.10.063 · 2.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Data indicated that zinc deficiency may contribute to the development of depression; however changes induced by zinc deficiency are not fully validated.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2014; DOI:10.1016/j.pnpbp.2014.09.013 · 4.03 Impact Factor