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

9 Citations (Scopus)

Abstract

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 31phosphor 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 levelsandphosphocreatine to inorganicphosphateratioremainedstable 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.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number2
ISSN0021-972X
DOIs
Publication statusPublished - 01.02.2011

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