Kavain, Dihydrokavain and Dihydromethysticin Non-Competitively Inhibit the Specific Binding of [³ H]-Batrachotoxinin-A 20-α-Benzoate to Receptor Site 2 of Voltage-Gated Na⁺ Channels

Abstract

The mode of action of the kava pyrones, kavain, dihydrokavain and dihydromethysticin on the specific binding of [³ H]-batrachotoxinin-A 20-α-benzoate to epitope 2 of voltage-dependent Na⁺ channels was investigated by performing saturation experiments in the presence and absence of these kava pyrones. The tested compounds significantly decreased the apparent total number of binding sites (B_max) for [³ H]-batrachotoxinin-A 20-α-benzoate (control: 0.5pmol/mg protein, kava pyrones: 0.2-0.27 pmol/mg protein) with little change in the equilibrium constants (K_D) for [³ H]-batrachotoxin-A 20-α-benzoate (control: 28.2 nM, kava pyrones: 24-31 nM). The results indicate for the kava pyrones a non-competitive inhibition of the specific [³H]-batrachotoxinin-A 20-α-benzoate binding to receptor site 2 of voltage-gated Na⁺ channels.