Recent clinical trials have shown that galantamine is efficacious in the treatment of mild to moderate Alzheimer's and vascular dementia, and memantine in severe stages of these diseases. Hence, the hypothesis that these two drugs might exert different degrees of neuroprotection has been tested. Rat hippocampal slices were subjected to oxygen and glucose deprivation (OGD) and to a re-oxygenation period. Neuronal damage was monitored using the lactate dehydrogenase (LDH) released into the Krebs-bicarbonate medium as an indicator. Galantamine, a mild acetylcholinesterase (AChE) blocker and nicotinic receptor modulator, given 30 min before and during OGD plus re-oxygenation (1, 2 and 3 h) significantly reduced LDH release by around 50%. Galantamine 5 microM reduced LDH release significantly during the re-oxygenation period while at 15 microM it afforded significant reduction of LDH release both during OGD and re-oxygenation. Memantine, a reversible blocker of NMDA receptors, at 10 microM only significantly reduced (40%) LDH release after 3 h re-oxygenation. The classical NMDA blocker MK-801 reduced LDH released around 40% at 1 microM at all re-oxygenation times studied. These data indicate that galantamine has a neuroprotective window against anoxia wider than memantine. Whether these differences can be clinically relevant remain to be studied in appropriate clinical trials.