Neuroprotective effect of memantine demonstrated in vivo and in vitro

The purpose of the present study was to test whether the anticonvulsant, memantine (1-amino-3,5-dimethyladamantane), can protect neurons against hypoxic or ischemic damage. To this end, we used a rat model of transient forebrain ischemia and cultured neurons from chick embryo cerebral hemispheres. Ischemia was induced for 10 min by clamping both carotid arteries and lowering the mean arterial blood pressure to 40 mm Hg; the rats were allowed to recover for 7 days. Cultured neurons were made hypoxic with 1 mmol/l NaCN added to the incubation medium for 30 min followed by a recovery period of 3 days. The possible effects of memantine were compared with those produced by a typical non-competitive NMDA antagonist, dizocilpine. Similar effects were obtained with both drugs. The drugs reduced the damage caused by transient ischemia to neurons of the hippocampal CA1 subfield. Memantine (10 and 20 mg/kg) had a dose-dependent effect when administered intraperitoneally to the rats 1 h before ischemia. Dizocilpine was active in this model at a dosage of 1 mg/kg. When administered after ischemia, 10 mg/kg memantine significantly protected CA1 neurons against ischemic damage. Furthermore, the drugs protected cultured neurons against hypoxic damage. The lowest effective concentration was 0.1 mumol/l for dizocilpine and 1 mumol/l for memantine. Thus, memantine possesses neuroprotective activity but is less potent than dizocilpine.