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 micromol/l (+)-kavain and 77 +/- 21, 90 +/- 14, 92 +/- 23 micromol/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.
Gleitz
J
J
University Clinics Ulm, Institute of Naturheilkunde, Helmholtzstr. 20, D-89081 Ulm, Germany.
Gottner
N
N
Ameri
A
A
Peters
T
T