HUPERZINE-A, A POTENTIAL THERAPEUTIC AGENT FOR DEMENTIA, REDUCES NEURONAL CELL-DEATH CAUSED BY GLUTAMATE

HUPERZINE A, a potential therapeutic agent for Alzheimer's disease, in hibits acetylcholinesterase in primary cultures derived from forebrain , hippocampus, cortex and cerebellum of embryonic rat brain. Glutamate induces cell death in cultures from all these brain regions. Maximum cell toxicity was observed in cerebellar cultures. Pretreatment of cel l cultures with Huperzine A reduced cell toxicity, as evidenced by cyt otoxicity assay and general morphology. Huperzine A pretreatment also reduced glutamate-induced calcium mobilization, but did not affect ele vations in intraneuronal free Ca2+ ([Ca](i)) caused by KCI or (-)Bay K 8644. The data suggest that Huperzine A could be a potent neuroprotec tive agent not only where cholinergic neurons are impaired, but also u nder conditions in which glutamatergic functions are compromised.