Characterization of the antinociceptive effects of a ganglioside derivative in rodents.

The results of a broad pharmacological screening on a natural mixture of gangliosides (GA) and an inner ester (AGF1) are reported. Up to relatively high doses, GA and AGF1 did not affect general behavior and neurologic functions and were devoided of diuretic, antipyretic, ulcerogenic, antireserpine, antiapomorphine, anticholinergic and anticonvulsivant actions. Both compounds interfere specifically with some induced conditions of inflammation and pain, but AGF1 shows a stronger action in reducing phenylquinone writhing than GA which appears to possess a more pronounced anti-inflammatory activity. In the rat paw oedema the anti-inflammatory effect of GA and AGF1 developed 1 hr after carrageenin and reached its maximum at 2 hr, suggesting that an inhibition of the serotonin and kinin phases might be partly responsible. Therefore, it would seem that the anti-inflammatory action of gangliosides is not exerted by an inhibition of the prostaglandin (PG) system. This assumption is supported by the finding that GA and AGF1 did not influence yeast-induced hyperthermia nor produced ulcerogenic effects in fasted rats. Subcutaneous administration of AGF1 is less potent than indomethacin (2 times) in reducing phenylquinone writhings, but more effective than GA (6 times), codeine (9 times) and acetylsalicylic acid (187 times). After i.c.v. administration the anti-writhing activity of AGF1 was far more potent than that of all the other compounds. The neuronal substrate involved in the AGF1 antinociception is unknown at this time. The comparative study with GA suggests a dissociation between the anti-inflammatory activity and the antinociceptive response. The lack of analgesia in the hot plate test and the naloxone insensitive anti-writhing effect of AGF1 in mice indicate that a central opioid mechanism is not involved in the antinociceptive action. Furthermore, the negativity of the neurogenic plasma extravasation test seems to exclude also an interaction with peripheral opiate receptors. It is suggested that the antinociceptive action of AGF1 has both a peripheral and a central component via an interference with peripheral exsudative phenomena and the central serotonergic tonus.