Vinpocetine selectively inhibits neurotransmitter release triggered by sodium channel activation.

The effects of vinpocetine on internal Na+ (Na(i)), cAMP accumulation, internal Ca2+ (Ca(i)) and excitatory amino acid neurotransmitters release, under resting and under depolarized conditions, was investigated in rat striatum synaptosomes. Veratridine (20 microM) or high K+ (30 mM) were used as depolarizing agents. Results show that vinpocetine in the low microM range inhibits the elevation of Na(i), the elevation of Ca(i) and the release of glutamate and aspartate induced by veratridine depolarization. In contrast, vinpocetine fails to inhibit the rise of Ca(i) and the neurotransmitter release induced by high K+, which are both TTX insensitive responses. Results also show that the inhibition exerted by vinpocetine on all the above veratridine-induced responses is not reflected in PDE activity. Our interpretation of these results is that vinpocetine inhibits neurotransmitter release triggered by veratridine activation of voltage sensitive Na+ channels, but not that triggered by a direct activation of VSCC. Thus, the main mechanism involved in the neuroprotective action of vinpocetine in the CNS is unlikely to be due to a direct inhibition of Ca2+ channels or PDE enzymes, but rather the inhibition of presynaptic Na+ channel-activation unchained responses.