Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects
Gerard Sanacora, Mark A. Smith, Sanjeev Pathak, H-L Su, Peter H. Boeijinga, Dennis J. McCarthy, Michael C. Quirk
Molecular Psychiatry October 15, 2013 DOI: 10.1038/mp.2013.130 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled study Peer reviewed |
|---|---|
| Interventions | AZD6765 (lanicemine) ketamine |
| Topics | Ketamine |
| Keywords | Psychotomimetic Nmda receptor Antidepressant Pharmacology Placebo Anesthesia Hippocampus |
| Citations | 234 |
| Key points | NMDA channel blockers can produce antidepressant efficacy without psychotomimetic and dissociative side effects, and the antidepressant response can be maintained with repeated and intermittent administration. |
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.