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 mu M) or high K+ (30 mM) were used as depolarizing agents. Results show that vinpocetine in the low mu M range inhibits the elevation of Nai, 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.