Glutamate-based antidepressants: 20 years on.
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.
Skolnick
Phil
P
Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA. phil.skolnick@nyumc.org
Popik
Piotr
P
Trullas
Ramon
R
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate