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, inhibits 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 cell cultures with Huperzine A reduced cell toxicity, as evidenced by cytotoxicity assay and general morphology. Huperzine A pretreatment also reduced glutamate-induced calcium mobilization, but did not affect elevations in intraneuronal free Ca2+ ([Ca](i)) caused by KCI or (-)Bay K 8644. The data suggest that Huperzine A could be a potent neuroprotective agent not only where cholinergic neurons are impaired, but also under conditions in which glutamatergic functions are compromised.