Memantine Prevents Hypoglycemia-Induced Decrements of the Cerebral Energy Status in Healthy Subjects

Willenborg, Bastian; Schmoller, André; Caspary, J.; Melchert, Uwe H.; Scholand-Engler, Harald G.; Jauch‐Chara, Kamila; Hohagen, Fritz; Schweiger, Ulrich; Oltmanns, Kerstin M.

doi:10.1210/jc.2010-1348

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…There may also be a rational basis for suggesting therapeutic value of memantine under conditions requiring improved frontal function. For example, 20 mg memantine acutely enhances cortical metabolic efficiency (Kim et al, 2010) and improves neurocognition after brain injury, and these effects are strongly associated with increased left frontal and parietal lobe glucose metabolism (Willenborg et al, 2011). We might predict that enhanced frontal cortical metabolic efficiency should have positive effects on frontal-regulated functions, such as sensorimotor gating and MMN, and that this effect might be particularly beneficial to patients whose frontal lobe efficiency is compromised by a disease process.…”

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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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: 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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“…Several lines of evidence suggest that MEM might have pro-cognitive effects in disorders other than dementias that are also characterized by cognitive deficits (Alizadeh et al 2015; Abbasinazari et al 2015). For example, MEM 20 mg acutely enhances cortical metabolic efficiency (Willenborg et al 2011) and improves neurocognition after brain injury, and these effects are strongly associated with increased left frontal and parietal lobe glucose metabolism (Kim et al 2010). To the degree that CPD is accompanied by dysregulation of cortical NMDA release (Javitt 2007; Deutsch et al 2001), one might predict that pharmacological interventions that selectively block excessive synaptic glutamate transmission might have beneficial effects for CPD patients.…”

Section: Introductionmentioning

confidence: 99%

Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy

et al. 2016

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Rationale Pro-cognitive agents for chronic psychotic disorders (CPDs) might be detected via experimental medicine models, in which neural targets engaged by the drug predict sensitivity to the drug’s pro-cognitive effects. Objective This study aims to use an experimental medicine model to test the hypothesis that “target engagement” predicts pro-cognitive effects of the NMDA antagonist, memantine (MEM), in CPDs. Methods MATRICS Consensus Cognitive Battery (MCCB) performance was assessed in CPD (n = 41) and healthy subjects (HS; n = 41) in a double-blind, randomized cross-over design of acute (single dose) MEM (placebo vs. 10 or 20 mg p.o.). Measures of prepulse inhibition (PPI) and mismatch negativity previously reported from this cohort substantiated target engagement. Biomarkers predicting MEM neurocognitive sensitivity were assessed. Results Testing confirmed MCCB deficits associated with CPD diagnosis, age, and anticholinergic exposure. MEM (20 mg p.o.) reduced MCCB performance in HS. To control for significant test order effects, an “order-corrected MEM effect” (OCME) was calculated. In CPD subjects, greater age, positive MEM effects on PPI, and SNP rs1337697 (within the ionotropic NMDA receptor gene, GRIN3A) predicted greater positive OCME with 20 mg MEM. Conclusions An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges. A single MEM 20 mg dose had a negative impact on neurocognition among HS. In CPD patients, age, MEM effects on PPI, and rs1337697 predicted sensitivity to the neurocognitive effects of MEM. Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients cannot be inferred without a validating clinical trial.

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“…Severe hypoglycemia causes hippocampal damage [5,6] activation of the N-methyl-d-aspartate, glutamate neurotoxicity, anoxic neuronal death and Amyloid-β neurotoxicity are implicated [7,8]. Animal model shows, Memantine, offering neuroprotective effects in hypoglycemic rats [9]. TBI leads neurochemical alterations [10] Similar to hypoglycemic injury, glutamatergic system is implicated [11,12] oxidative stress is also implicated [13] antioxidants has proved to be beneficial [14,15] .…”

Section: Neuroprotection Versus Neurotoxicitymentioning

confidence: 99%

Psychotropics and Neuroprotection: Literature Review and Case Series Report

Meresh¹,

Daniels²,

Owens³

et al. 2019

obm neurobiol

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Agitation is a common manifestation of acute brain injury. When not addressed, agitation can lead to slower recovery rates, including delayed admission to acute rehabilitation programs. Antipsychotics are commonly used to control agitation in acute brain injury in the ICU. However, there is no current consensus on the most "efficacious and safest strategy" for use of antipsychotics in acute TBI. Haloperidol is arguably the commonly used antipsychotic for agitation in ICU setting at present. Interestingly, there are no studies to our knowledge that assess for haloperidol use in TBI patient's specifically. Further, there are some concerns with the use of Haloperidol given that it does not offer a neuroprotective effect and may have some adverse effects that are particularly harmful for this population. In this paper, we offer a review of alternate medications that may be more appropriate for the treatment of

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Memantine Prevents Hypoglycemia-Induced Decrements of the Cerebral Energy Status in Healthy Subjects

Cited by 13 publications

References 17 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

Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy

Psychotropics and Neuroprotection: Literature Review and Case Series Report

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