| Abstrakt: |
The moderate affinity uncompetitive NMDA receptor antagonist memantine, at concentrations found to be neuroprotective in animal models of chronic excitotoxicity, did not reduce ischaemic tolerance induced chemically with 3 nitropropionic acid (3-NP), but actually tended to enhance this effectex vivo. Injection of 3-NP (20 mg/kg i.p.) — 24 h prior to thein vitroexperiment — significantly protected against hypoxia/hypoglycaemia-induced suppression of extracellular field excitatory postsynaptic potentials (fEPSPs) in rat hippocampal slices (62.2% vs. control of 16.8%), whereas 3 days pretreatment with memantine (20 mg/kg/day —Alzet minipumps) tended to enhance recovery further following 3-NP preconditioning (89.7%). This low dose of memantine had no effect on fEPSPs in the absence of preconditioning. As expected, 3 days pretreatment with a high dose of (+)MK-801 (dizocilpine; 2mg/kg/day-Alzet minipumps) tended to reduce ischaemic tolerance following 3-NP preconditioning (45.3%). We conclude that although NMDA receptors do seem to be involved in chemically-induced ischaemic tolerance, semi-chronic pre-treatment with therapeutically-relevant doses of memantine does not block ischameic tolerance. |
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