MEMANTINE INDUCES HEAT-SHOCK PROTEIN HSP70 IN THE POSTERIOR CINGULATECORTEX, RETROSPLENIAL CORTEX AND DENTATE GYRUS OF RAT-BRAIN

High-affinity N-methyl-D-aspartate (NMDA) receptor antagonists like MK -801 are known to induce the heat shock protein, HSP70, in the posteri or cingulate cortex and retrosplenial cortex of rat brain. Memantine, which is a low affinity uncompetitive NMDA receptor antagonist, has be en used in the treatment of Parkinson's disease in Europe. The faster kinetics of memantine in blocking and unblocking the NMDA receptor-ope rated ion channel as opposed to high-affinity NMDA antagonists like MK -801 has been thought to account for the safety of memantine. The pres ent study evaluated the neurotoxic potential of memantine and amantadi ne using the induction of HSP70 immunoreactivity in rat brain, Memanti ne (25, 50, 75 mg/kg) induced HSP70 in the posterior cingulate, retros plenial cortex and dentate gyrus of rat brain. In contrast, amantadine (50, 100, 200 mg/kg) did not induce HSP70 in the rat brain. These res ults suggest that memantine has an antagonistic effect at NMDA recepto r in vivo, and raises the possibility that high doses of memantine may cause neuronal damage similar to those observed with other high-affin ity NMDA receptor antagonists.