Kavain Inhibits Non-Stereospecifically Veratridine-Activated Na⁺ Channels

Abstract

The action of the natural kava pyrone, (+)-kavain, and its synthetic racemate, (±)-kavain, on voltage-dependent Na⁺ channels was investigated, while considering their stereospecific properties, on veratridine-induced increases in cytosolic free Na⁺ and Ca²⁺ ([Na⁺]_i, [Ca²⁺]_i) and the release of endogenous glutamate from cerebrocortical synaptosomes. Both compounds dose-dependently suppressed the veratridine-induced increase in [Na⁺]_i, [Ca²⁺]_i and glutamate release with IC₅₀ values (± S.D.) of 71 ± 22, 72 ± 7, 120 ± 37 µmol/l (+)-kavain and 77 ± 21, 90 ± 14, 92 ± 23 µmol/l (±)-kavain, respectively. As judged from the dose-dependency, IC₅₀ values, velocity and time course of action, both kava pyrones were equally effective suggesting a non-stereospecific inhibition of veratridine-activated Na⁺ channels.