NEUROPROTECTION BY MEMANTINE AS INCREASED BY HYPOTHERMIA AND NIMODIPINE

The aim of the present study was to demonstrate the neuroprotective ac tivity of memantine and its augmentation by hypothermia and by the cal cium antagonist nimodipine. The mouse model of permanent focal cerebra l ischemia and the rat model of reversible global forebrain ischemia w ere used. In both models a protective effect of memantine against dama ge of brain tissue caused by ischemia was demonstrable, the potency of memantine being lower than that of dizocilpine. Highly pronounced neu roprotection was obtained when memantine (10 mg/kg) was administered t o the rats in hypothermia (85% damage of the hippocampal CAI neurons i n normothermic control rats compared to 15% damage in hypothermic rats treated with memantine). A dose-dependent neuroprotective effect of m emantine was also measurable in primary cultures of rat hippocampal ne urons treated with 1 mmol/l glutamate. Nimodipine (10 nmol/l) added to the culture medium shifted the dose-response curve of memantine more effectively to the left as it was precalculated, suggesting an over-ad ditive neuroprotective effect of both these drugs. The results present ed provide strong evidence for the neuroprotective activity of memanti ne. This activity was increased by hypothermia in the global ischemia model and by nimodipine in cultured rat hippocampal neurons. Therefore , memantine is suggested as a promising drug with moderate side effect s for stroke and dementia therapy.