Kavain inhibits non-stereospecifically veratridine-activated Na+ channels

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 mu mol/l (+)-kavain and 77 +/- 21, 90 +/- 14, 92 +/- 23 mu mol/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.