The neuroprotective drug vinpocetine prevents veratridine-induced [Na+]i and [Ca2+]i rise in synaptosomes.
The effect of the neuroprotective drug, vinpocetine on the veratridine-evoked [Na+]i and [Ca2+]i rise in isolated nerve terminals was studied. Vinpocetine, in a pharmacologically relevant concentration range (0.4-10 microM)i reduced the increase of [Na+]i induced by veratridine (100 microM). The effect of the drug was concentration-dependent with 10 microM vinpocetine completely preventing the increase of [Na+]i. The [Ca2+]i rise in response to veratridine was also prevented by vinpocetine. In addition, the [Ca2+]i signal induced by depolarization with 20 mM K+ was reduced by vinpocetine (1-20 microM). This effect was not influenced by preincubation with 1 microM TTX and was also observed when Na+ was replaced by N-methyl glucamine in the medium. It is concluded that vinpocetine is capable of inhibiting voltage-dependent Na+ and Ca2+ channels, respectively, and these effects might contribute to the neuroprotection exerted by the drug.
Department of Medical Biochemistry, Semmelweis University of Medicine, Budapest, Hungary.
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Tretter
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Adam-Vizi
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D018696:Neuroprotective Agents; D014748:Vinca Alkaloids; C013983:vinpocetine; D014701:Veratridine; D012964:Sodium; D002118:Calcium