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Memantine prevents hypoglycemia-induced decrements of the cerebral energy status in healthy subjects.

Author(s): Willenborg B, Schmoller A, Caspary J, Melchert UH, Scholand-Engler HG, Jauch-Chara K, Hohagen F, Schweiger U, Oltmanns KM

Affiliation(s): Department of Psychiatry and Psychotherapy, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. bastian.willenborg@uk-sh.de

Publication date & source: 2011-02, J Clin Endocrinol Metab., 96(2):E384-8. Epub 2010 Nov 24.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

CONTEXT: The risk to develop dementia is significantly increased in diabetes mellitus. Memantine, an N-methyl-D-aspartate receptor antagonist, which is clinically applied in dementia, has been shown to exert neuroprotective effects under hypoglycemic conditions in rats. OBJECTIVE: We hypothesized that memantine may prevent hypoglycemia-induced decrements in the cerebral high-energy phosphate, i.e. ATP, metabolism to exert its neuroprotective action under these conditions. DESIGN AND PARTICIPANTS: In a randomized, double-blind crossover design, we applied memantine vs. placebo in 16 healthy male subjects and examined the cerebral high-energy phosphate metabolism by (31)phosphor magnetic resonance spectroscopy, hormonal counterregulation, and neurocognitive performance during hypoglycemic glucose clamp conditions. RESULTS: We found increments in hormonal counterregulation and reduced neurocognitive performance during hypoglycemia (P < 0.05). Cerebral ATP levels increased upon hypoglycemia in the memantine condition as compared with placebo (P = 0.006) and remained higher after renormalizing blood glucose concentrations (P = 0.018), which was confirmed by ATP to inorganic phosphate ratio (P = 0.046). Phosphocreatine levels and phosphocreatine to inorganic phosphate ratio remained stable throughout the experiments and did not differ between conditions (P > 0.1 for both). CONCLUSION: Our data demonstrate that memantine preserves the cerebral energy status during experimentally induced hypoglycemia in healthy subjects. An improved neuronal energy status may thus be involved in the neuroprotective effect under these conditions and may qualify memantine as potential future option to combat cognitive impairments and dementia in diabetes.

Page last updated: 2011-12-09

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