dizocilpine-maleate and Hyperinsulinism

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.. 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.. 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.. 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).. 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.

Topics: Adenosine Triphosphate; Adult; Blood Glucose; Brain Chemistry; Cross-Over Studies; Dizocilpine Maleate; Double-Blind Method; Energy Metabolism; Glucose Clamp Technique; Hormones; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Magnetic Resonance Imaging; Male; Memantine; Memory, Short-Term; Neuroprotective Agents; Phosphorus Isotopes; Stroop Test; Young Adult