Description:
<jats:title>Abstract</jats:title>
<jats:p>Roots of kava (<jats:italic>Piper methysticum</jats:italic>) plant are used in almost all Pacific Ocean cultures to prepare a drink with sedative, anesthetic and euphoric properties. One of the main active ingredients of the extract are kava lactones. Here, kava root CO<jats:sub>2</jats:sub> extract and three kavalactones, DL-kavain, dihydrokavain and yangonin (isolated from whole extract by column chromatography) were tested for their inhibitory action on recombinant homomeric human α1 glycine receptors expressed in HEK293 cells. Kava CO<jats:sub>2</jats:sub> root extract, as well as the individual components DL-kavain, dihydrokavain and yangonin inhibited glycine receptor activity in a dose-dependent manner. DL-kavain was the most potent inhibitor (IC<jats:sub>50</jats:sub> = 0.077 ± 0.002 m<jats:sc>m</jats:sc>), followed by yangonin (IC<jats:sub>50</jats:sub> = 0.31 ± 0.04 m<jats:sc>m</jats:sc>) and dihydrokavain (IC<jats:sub>50</jats:sub> = 3.23 ± 0.10 m<jats:sc>m</jats:sc>) which were 4- and 40-fold less active than DL-kavain, respectively. Application of kava root extract did not reduce maximum currents, but increased EC<jats:sub>50</jats:sub> of glycine. Simultaneous application of kava extract and strychnine showed additive inhibition, suggesting that binding of kavalactones and strychnine on the receptor is mutually exclusive. Overall, kavalactones exert a moderate inhibitory effect on the human α1 glycine receptor with DL-kavain being the most potent constituent.</jats:p>