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

• Published in: Journal of psychopharmacology (Oxford) 2012-11, Vol.26 (11), p.1417-1423
• Main Authors: Pringle, A, Parsons, E, Cowen, LG, McTavish, SF, Cowen, PJ, Harmer, CJ
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Amino acids; Antagonist drugs; Antidepressants; Antidepressive Agents - pharmacology; Biological and medical sciences; Citalopram - pharmacology; Clinical trials; Depression; Double-Blind Method; Emotions; Excitatory Amino Acid Antagonists - pharmacology; Humans; Indexing in process; Male; Medical sciences; Memantine - pharmacology; Memory, Short-Term - drug effects; Mental depression; Mood disorders; Neuropharmacology; Neuropsychological Tests; Neuropsychology; Original Papers; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Reflex, Startle - drug effects; Serotonin Uptake Inhibitors - pharmacology; Young Adult
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881112446535

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.