title: Using an experimental medicine model to understand the antidepressant potential of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantine.
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.
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK. abbie.pringle@psych.ox.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Pringle
authors.forename: E
authors.initials: E
authors.lastname: Parsons
authors.forename: L G
authors.initials: LG
authors.lastname: Cowen
authors.forename: S F
authors.initials: SF
authors.lastname: McTavish
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: C J
authors.initials: CJ
authors.lastname: Harmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology; D004311:Double-Blind Method; D004644:Emotions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D016194:Receptors, N-Methyl-D-Aspartate; D017367:Selective Serotonin Reuptake Inhibitors