VINPOCETINE IS A HIGHLY POTENT NEUROPROTECTANT AGAINST VERATRIDINE-INDUCED CELL-DEATH IN PRIMARY CULTURES OF RAT CEREBRAL-CORTEX

The effects of vinpocetine and phenytoin against veratridine-induced cell death were investigated in primary cultures of rat cerebral cortex. Toxicity was evaluated by phase contrast microscopy and quantified by measuring lactic dehydrogenase leakage from damaged cells. Vinpocetine was highly potent in inhibiting the cell death evoked by veratridine. The concentrations of the drug evoking 50% protection (IC50 values) against 100 mu M (maximal response) and 50 mu M (half-maximal response) veratridine were 490 nM and 63 nM, respectively. The protective efficacy of vinpocetine exceeded about 100-fold that of phenytoin (IC50 = 44.2 mu M against 100 mu M veratridine), a prototype sodium-channel blocker. These data suggest that the blockade of voltage-gated sodium channels is a possible mechanism of action for the well-known neuroprotective and anticonvulsant properties of vinpocetine.