We attempted to elucidate the antitussive principles of Glycyrrhizae radix, a main component of Bakumondo-to (Mai-men-dong-tang). Although the 50% methanol-eluted fraction (100 mg/kg, p.o.) caused a more than 60% reduction in the number of capsaicin-induced coughs, neither the water-eluted nor 100% ethanol-eluted fractions of water extract of G. radix had antitussive effects. The water extract of G. radix contained high levels of liquiritin, liquiritin apioside, isoliquiritin, isoliquiritin apioside and glycyrrhizin. On the other hand, the 50% methanol-eluted fraction contained mainly liquiritin and liquiritin apioside, but not the other compounds. Liquiritin apioside (3-30 mg/kg, p.o.), but not liquiritin, isoliquiritin, isoliquiritin apioside or glycyrrhizin, dose-dependently inhibited the number of coughs. Methysergide, a serotonin receptor antagonist, antagonized the antitussive effect of liquiritin apioside. However, the antitussive effect of liquiritin apioside was not antagonized by naloxone. Pretreatment with glibenclamide (3 mg/kg, i.p.), an ATP-sensitive potassium channel blocker, also significantly reduced the antinociceptive effect of liquiritin apioside. These results suggest that G. radix contains a potent antitussive compound, liquilitin apioside, whose antitussive effect may depend on both peripheral and central mechanisms.