Using an experimental medicine model to understand the antidepressant potential of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine

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#adolescent #adult #antidepressive-agents #citalopram #double-blind-method

Using an experimental medicine model to understand the antidepressant potential of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine

Pringle et al., 2012 | J Psychopharmacol | Rct

Citation

Pringle A, Parsons E, ... Harmer C J. Using an experimental medicine model to understand the antidepressant potential of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine. J Psychopharmacol. 2012-Nov;26(11):1417-23. doi:10.1177/0269881112446535

Abstract

There is growing interest in the role of the glutamatergic system both in depression and as a novel target for treatments. Preclinical studies suggested that the non-competitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine might have antidepressant properties, but a randomised controlled trial failed to support this. A healthy volunteer model of emotional processing was used to assess the neuropsychological profile of action of memantine. Healthy volunteers (n=32) were randomised to receive a single dose of memantine (10 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory, dot-probe and emotion-potentiated startle tasks, as well as working and verbal memory. Memantine treated volunteers showed an increased emotion-potentiated startle, and a reduced bias for negative items in emotional recognition memory. There were no effects of the drug on any other aspect of emotional or non-emotional information processing. These results suggest that a single dose of memantine produces an early anxiogenic response in the emotion-potentiated startle similar to that seen following a single dose of the selective serotonin reuptake inhibitor, citalopram. However, the overall profile of effects is more limited than that which might be expected in response to a conventional antidepressant.

Key Findings

However, the overall profile of effects is more limited than that which might be expected in response to a conventional antidepressant.

Outcomes Measured

  • depression

Population

Field Value
Population See abstract
Sample Size 32
Age Range See abstract
Condition depression

MeSH Terms

  • Adolescent
  • Adult
  • Antidepressive Agents
  • Citalopram
  • Double-Blind Method
  • Emotions
  • Excitatory Amino Acid Antagonists
  • Humans
  • Male
  • Memantine
  • Memory, Short-Term
  • Neuropsychological Tests
  • Receptors, N-Methyl-D-Aspartate
  • Reflex, Startle
  • Selective Serotonin Reuptake Inhibitors
  • Young Adult

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
  • Vertical: d-aspartic-acid

Provenance

Source extracted via PubMed E-utilities API on 2026-04-12