Original Article

Molecular Psychiatry (2014) 19, 978–985; doi:10.1038/mp.2013.130; published online 15 October 2013

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects
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G Sanacora1, M A Smith2, S Pathak2, H-L Su2, P H Boeijinga3, D J McCarthy2 and M C Quirk4

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

Correspondence: Dr G Sanacora, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park Street, 333 A, New Haven, CT 06519, USA. E-mail: gerard.sanacora@yale.edu

Received 22 April 2013; Revised 17 June 2013; Accepted 1 August 2013
Advance online publication 15 October 2013

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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.

Keywords:

antidepressant efficacy; lanicemine; NMDA channel blocker