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Antidepressant Drug Targets Brain Receptors in New Way

Novel compound modulates receptors responsible for learning and memory (Dec. 6)

A first-of-its-kind antidepressant drug discovered at Northwestern University has been shown to alleviate symptoms within hours in adults who failed other antidepressant therapies. The new drug, called GLYX-13, targets brain receptors responsible for learning and memory — a different approach from existing antidepressants.

Results from the phase IIa clinical study were presented at the 51st Annual Meeting of the American College of Neuropsychopharmacology in Hollywood, Florida, and background scientific research that provided the foundation for the clinical development of GLYX-13 was published in Neuropsychopharmacology.

GLYX-13 works by modulating N-methyl-D-aspartate (NMDA) receptors in the brain, as do current NMDA receptor antagonists, such as ketamine — but GLYX-13 does not have the serious and limiting side effects of those drugs, such as hallucinations and schizophrenia-like effects, the researchers say.

In clinical trials, a single dose of GLYX-13 significantly reduced depression symptoms in subjects who had failed treatment with one or more antidepressant agents. The positive effects of GLYX-13 were evident within 24 hours and lasted an average of 7 days. The effect size — a measure of the magnitude of the drug’s antidepressant efficacy — at both of these time points after a single dose was nearly double the effect size seen with most other antidepressant drugs after 4 to 6 weeks of repeated dosing.

The side effects of GLYX-13 were mild to moderate in severity and were similar to those observed in subjects receiving placebo.

GLYX-13 is a four–amino-acid peptide that modulates one of a large family of glutamate receptors — the NMDA receptors — in the brain. NMDA receptors play a key role in regulating synaptic plasticity (the quality of the connection between neurons) and are important in regulating learning and memory functions.

GLYX-13 is administered intravenously, but the researchers are also working to develop an oral formulation with similar properties.

A phase IIb clinical trial is evaluating repeated doses of the drug.

Source: Northwestern University; December 6, 2012.

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