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Mol Psychiatry. 2014 Sep;19(9):978-85. doi: 10.1038/mp.2013.130. Epub 2013 Oct 15.

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

Author information

1
Clinical Neuroscience Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
2
AstraZeneca Pharmaceuticals LP, R&D, Wilmington, DE, USA.
3
FORENAP, Rouffach, France.
4
AstraZeneca R&D, Boston, MA, USA.

Abstract

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00491686 NCT00781742 NCT01130909.

PMID:
24126931
PMCID:
PMC4195977
DOI:
10.1038/mp.2013.130
[Indexed for MEDLINE]
Free PMC Article
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