Effects of NMDA receptor antagonist memantine on mismatch negativity

Korostenskaja, Milena; Nikulin, Vadim V.; Kičić, Dubravko; Nikulina, Anna V.; Kähkönen, Seppo

doi:10.1016/j.brainresbull.2007.01.007

Cited by 74 publications

(56 citation statements)

References 84 publications

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“…In previous reports in HS, acute exposure to NMDA antagonists led to greater levels of both PPI (Duncan et al, 2001;Abel et al, 2003;Swerdlow et al, 2002bSwerdlow et al, , 2009 and-in the case of memantine-MMN (Korostenskaja et al, 2007), but the present findings provide the first evidence for such effects in CPD patients. Conceivably, NMDA activity might be deficient within substrates responsible for core CPD symptoms, but be normal or even elevated in other brain regions regulating PPI and MMN.…”

Section: Discussioncontrasting

confidence: 51%

“…Thus, PPI is actually increased in healthy subjects (HS) by NMDA antagonists such as ketamine (Duncan et al, 2001;Abel et al, 2003), the low-to moderate-affinity NMDAreceptor antagonist, memantine (Swerdlow et al, 2009), and by the mixed NMDA antagonist/dopamine agonist, amantadine (Swerdlow et al, 2002b). Although MMN has been reported to be reduced in HS by ketamine (Umbricht et al, 2000;Umbricht et al, 2002), it has also been shown to be increased by memantine (Korostenskaja et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

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Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n = 84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients.

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Section: Discussioncontrasting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

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“…27 In contrast to ketamine, other psychotomimetic agents such as psilocybin 28 or LSD 29 do not disrupt MMN, although they do impair generation of other, frontoparietally generated potentials (eg, P3). Conversely, memantine, a compound that is often classified as an NMDAR antagonist but paradoxically does not produce psychosis in humans, 30 also paradoxically enhances MMN in humans 31 despite blocking MMN generation in rodents, 32 suggesting that MMN is sensitive to the net neurophysiological events associated with psychosis and cognitive impairments in humans, rather than to the a priori classification of a drug based on animal models.…”

Section: Nmdar Contributions To Dopaminergic Dysfunction Inmentioning

confidence: 99%

Has an Angel Shown the Way? Etiological and Therapeutic Implications of the PCP/NMDA Model of Schizophrenia

Javitt

Zukin²,

Heresco-Levy

et al. 2012

Schizophrenia Bulletin

280

203

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“…Although no source modeling was used, it is possible that glycine has different effects on supratemporal vs frontal MMN generators, which may explain the unexpected findings. Korostenskaja et al (2007) showed that the NMDA antagonist memantine increased MMN amplitude without otherwise changing ERP components. This effect of memantine was observed only in EEG but not in MEG, suggesting that memantine has effects on frontal but not temporal MMN components.…”

Section: Bottom-up: Change Detectionmentioning

confidence: 99%

How Human Electrophysiology Informs Psychopharmacology: from Bottom-up Driven Processing to Top-Down Control

Kenemans

Kähkönen

2010

Neuropsychopharmacol

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This review surveys human event-related brain potential (ERP) and event-related magnetic field (ERF) approaches to psychopharmacology and psychopathology, and the way in which they complement behavioral studies and other neuroimaging modalities. The major paradigms involving ERP/ERF are P50 suppression, loudness-dependent auditory evoked potential (LDAEP), mismatch negativity (MMN), P300, mental chronometry, inhibitory control, and conflict processing (eg, error-related negativity (ERN)). Together these paradigms cover a range of more bottom-up driven to more top-down controlled processes. A number of relationships between the major neurotransmitter systems and electrocortical mechanisms are highlighted. These include the role of dopamine in conflict processing, and perceptual processing vs motor preparation; the role of serotonin in P50 suppression, LDAEP, and MMN; glutamate/NMDA and MMN; and the role of acetylcholine in P300 generation and memory-related processes. A preliminary taxonomy for these relationships is provided, which should be helpful in attuning possible new treatments or new applications of existing treatments to various disorders.

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Effects of NMDA receptor antagonist memantine on mismatch negativity

Cited by 74 publications

References 84 publications

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Has an Angel Shown the Way? Etiological and Therapeutic Implications of the PCP/NMDA Model of Schizophrenia

How Human Electrophysiology Informs Psychopharmacology: from Bottom-up Driven Processing to Top-Down Control

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