Kavain, Dihydrokavain and Dihydromethysticin Non-Competitively Inhibit the Specific Binding of [³H]-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 [3H]-batrachotoxinin-A 20-alpha-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 (Bmax) for [3H]-batrachotoxinin-A 20-alpha-benzoate (control: 0.5 pmol/mg protein, kava pyrones: 0.2-0.27 pmol/mg protein) with little change in the equilibrium constants (KD) for [3H]-batrachotoxin-A 20-alpha-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-alpha-benzoate binding to receptor site 2 of voltage-gated Na+ channels.

Kava treatment in patients with anxiety

“…Studies have been contradictory regarding its GABA-receptor-binding capacity (Jussofie et al, 1994;Davies et al, 1992). However, a major mechanism in anticonvulsive, analgesic and centrally muscle relaxing effects is assumed to be the blockage of voltage-gated sodium and calcium channels (Schirrmacher et al, 1999;Friese and Gleitz, 1998;Gleitz et al, 1995) which thus suppresses the release of endogenous glutamate (Gleitz et al, 1996). Additional psychotropic effects may be due to influences on neurotransmitter metabolism by blocking of MAO-B (Uebelhack et al, 1998), the activation of mesolimbic dopaminergic neurons or effects on 5-serotonin levels (Baum et al, 1998).…”

Extracts of kava ( Piper methysticum ) induce acute anxiolytic-like behavioral changes in mice

“…The mechanisms of kava's pharmacological effect are not well characterized, nor is it clear which kava lactones are responsible for the various pharmacological effects observed. Kava's anticonvulsant properties have been linked to its interaction with the voltage-gated sodium and calcium channels (Gleitz et al 1996;Maura et al 1997;Friese and Gleitz 1998;Schirrmacher et al 1999). Kava's anxiety-reducing effects have been suggested to be due to its interactions with the GABA A receptor; however, data supporting this conjecture are equivocal (Davies et al 1992;Jussofie et al 1994;Boonen and Häberlein 1998;Dinh et al 2001).…”

Kava toxicity

“…It has been postulated that they may exert their effects on inhibiting voltage‐dependent sodium channels. 4–6 Other experiments suggest they may have their effect on gamma‐aminobutyric acid (GABA), benzodiazepine receptors and dopamine receptors. Overall, however, little is known about the mode of action of kavalactones.…”