Amico-Roxas M, Caruso A, Cioni M, Scifo R, Leone M G, Scapagnini U
Institute of Pharmacology, University of Catania Medical School, Italy.
Arch Int Pharmacodyn Ther. 1988 Jan-Feb;291:238-52.
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.
报道了对神经节苷脂（GA）和一种内脂（AGF1）的天然混合物进行广泛药理筛选的结果。直至相对高剂量，GA和AGF1均不影响一般行为和神经功能，且无利尿、退热、致溃疡、抗利血平、抗阿扑吗啡、抗胆碱能和抗惊厥作用。两种化合物均特异性地干扰某些诱导的炎症和疼痛状态，但AGF1在减轻苯醌扭体反应方面比GA表现出更强的作用，而GA似乎具有更明显的抗炎活性。在大鼠足爪水肿模型中，GA和AGF1的抗炎作用在角叉菜胶注射后1小时出现，并在2小时达到最大，提示对5-羟色胺和激肽阶段的抑制可能部分起作用。因此，神经节苷脂的抗炎作用似乎不是通过抑制前列腺素（PG）系统发挥的。这一假设得到以下发现的支持：GA和AGF1既不影响酵母诱导的体温过高，也不在禁食大鼠中产生致溃疡作用。皮下注射AGF1在减轻苯醌扭体反应方面比吲哚美辛（2倍）效力低，但比GA（6倍）、可待因（9倍）和乙酰水杨酸（187倍）更有效。脑室内注射后，AGF1的抗扭体活性比所有其他化合物都强得多。此时，AGF1抗伤害感受所涉及的神经元底物尚不清楚。与GA的比较研究表明抗炎活性和抗伤害感受反应之间存在分离。在热板试验中缺乏镇痛作用以及AGF1对小鼠的抗扭体作用对纳洛酮不敏感，表明中枢阿片类机制不参与抗伤害感受作用。此外，神经源性血浆外渗试验的阴性结果似乎也排除了与外周阿片受体的相互作用。提示AGF1的抗伤害感受作用通过干扰外周渗出现象和中枢5-羟色胺能张力而同时具有外周和中枢成分。
