The effect of majonoside-R2 on morphine- and U-50,488H-induced antinociception was examined by the tail-pinch test in mice and compared with that of diazepam. Majonoside-R2 and diazepam inhibited the morphine- and U-50,488H-induced antinociception, and the actions were antagonized by the benzodiazepine receptor antagonist flumazenil and the GABA-gated Cl- channel blocker picrotoxin. Diazepam but not majonoside-R2 exhibited a protective activity against convulsion caused by the GABA(A) antagonists bicuculline and picrotoxin. These results indicate that GABA(A) systems are involved in the effect of majonoside-R2 on the opioid-induced antinociception and suggest that the mechanisms of action of majonoside-R2 may differ from those of diazepam.
