Mipragoside

The effect of AGF 44, an ester derivative of ganglioside GM1, on formalin-induced nociceptive behavior was examined in normal and streptozotocin-diabetic rats. AGF 44 (30 mg/kg/day i.p. for 7 days) produced a significant reduction of the second phase (20-40 min) and a lesser degree of suppression of the first phase (1-2 min) of the formalin test in both control and diabetic rats. Diabetic rats showed an increased response during the quiescent period (5-16 min) which was ameliorated by treatment with AGF 44 (30 mg/kg i.p.) for the last 7 days of a 5 week period of diabetes. These results indicate that AGF 44 can diminish responses to a prolonged nociceptive stimulus in both normal and diabetic rats and reduces the exaggerated nociceptive behavior of diabetic rats.

We evaluated the pharmacodynamic and pharmacokinetic profile of Mipragoside, a monosialoganglioside isopropyl-ester (as 0.5% w/w ophthalmic gel), on allergic inflammation of the eye induced by reverse passive Arthus reaction, on a non-immune mast cell degranulation elicited by compound 48/80 and on ocular inflammation produced by horse serum. Conjunctiva was sensitized by injection of rabbit antisera to bovine proteins and the allergic conjunctivitis was triggered by intravenous administration of bovine gamma globulin. The permeability of the blood-conjunctival barrier was evaluated by a fluorometric method. Compound 48/80 was topically administered at concentration of 50mg/ml and histological analysis of conjunctiva was performed. Horse serum was administered by intravenous injection at different days. The pharmacokinetic profile of topical 3H-Mipragoside on 48/80 model was investigated and compared with untreated animals. Mipragoside treatment significantly reduced (p < 0.05 vs placebo) the conjunctival vasopermeability induced by reverse passive Arthus reaction as well as successfully reduced the eosinophil levels in the conjunctival epithelium (p < 0.01 vs placebo) elicited by compound 48/80. Further, Mipragoside successfully reduced the primary signs of ocular inflammation produced by horse serum administration. A radiotracer technique was used to evaluate the disposition of 3H-Mipragoside in the rabbit ocular tissues. Disposition of the drug was monitored at 30, 60, 120 and 240 min. 3H-Mipragoside levels in the inflamed conjunctiva were significantly higher (p < 0.01) than in the control eye.