The nootropic drug vinpocetine inhibits veratridine-induced [Ca2+](i) increase in rat hippocampal CA1 pyramidal cells

The alkaloid derivative vinpocetine (14-ethoxycarbonyl-(3 alpha, 16 alpha - ethyl)-14,15-eburnamine; Cavinton) has a well known beneficial effect on br ain function in hypoxic and ischemic conditions. While it increases CNS blo od flow and improves cellular metabolism, relatively little is known about vinpocetine's underlying molecular mechanisms on the single cell level. Sin ce apoptotic and necrotic cell damage is always preceded by an increase in [Ca2+](i), this study investigated the effect of vinpocetine on [Ca2+](i) i ncreases in acute brain slices. Sodium influx is an early event in the bioc hemical cascade that takes place during ischemia. The alkaloid veratridine can activate this Na+ influx, causing depolarization and increasing [Ca2+]( i) in the cells. Therefore, it can be used to simulate an ischemic attack i n brain cells. Using a cooled CCD camera-based ratio imaging system and cel l loading with fura 2/AM, the effect of vinpocetine on [Ca2+](i) changes in single pyramidal neurons in the vulnerable CAI region of rat hippocampal s lices was investigated. Preperfusion and continuous administration of vinpo cetine 10 muM) significantly inhibited the elevation in [Ca2+](i) induced b y veratridine (10 muM). When the drug was administered after veratridine, i t could accelerate the recovery of cellular calcium levels. Piracetam, anot her nootropic used in clinical practice, could attenuate the elevation of [ Ca2+](i) only at a high, 1 mM, concentration. We have concluded that vinpoc etine, at a pharmacologically relevant concentration, can decrease patholog ically high [Ca2+](i) levels in individual rat hippocampal CAI pyramidal ne urons; this effect might contribute to the neuroprotective property of the drug.