g(m1)-ganglioside and mipragoside

To evaluate the efficacy of Mipragoside, a ganglioside derivative, in vernal keratoconjunctivitis we performed a controlled randomised clinical trial involving 24 patients (mean age 10 +/- 3.4 years, range 5-20 years). Patients received either Mipragoside 0.5% aqueous ophthalmic gel or placebo four times a day for 2 weeks after a week of treatment with placebo. Ocular signs and symptoms were evaluated and considered for statistical analysis. Results show that Mipragoside significantly reduces all symptoms, being most effective on itching (p = 0.01; p = 0.0001) and hyperaemia (p = 0.01; p = 0.0006) after 1 and 2 weeks respectively when compared with placebo. Physician judgement of drug efficacy at the end of treatment was significantly in favour of Mipragoside (p = 0.0001) compared with placebo. We conclude that Mipragoside topical treatment improves symptoms of patients with vernal keratoconjunctivitis and we postulate a possible anti-inflammatory activity of this compound.

Topics: Administration, Topical; Adolescent; Adult; Child; Child, Preschool; Conjunctivitis, Allergic; Female; G(M1) Ganglioside; Gels; Humans; Male; Treatment Outcome

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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Transport, Active; Cell Membrane Permeability; Conjunctiva; Conjunctivitis, Allergic; Corneal Opacity; Fluorophotometry; G(M1) Ganglioside; Gels; Hyperemia; Iris; Male; Rabbits

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.

Topics: Animals; Behavior, Animal; Diabetes Mellitus, Experimental; Escape Reaction; Female; Formaldehyde; G(M1) Ganglioside; Male; Nociceptors; Pain; Rats; Rats, Sprague-Dawley

Gangliosides (GA) have been shown to promote axonal sprouting and growth of injured peripheral nerves, and enhance functional biochemical and morphologic recovery after CNS damage. Moreover, it has recently been shown that the natural ganglioside mixture (GM1 + GD1a + GD1b + GT1b) from bovine brain is endowed with powerful anti-inflammatory activity in rodents. Here we report that the novel semisynthetic ganglioside derivative AGF44, the isopropyl ester of monosialoganglioside GM1, displays a potent anti-inflammatory activity when orally or topically administered in various models of acute inflammation. AGF44 was effective (0.5-5 mg/kg p.o. or 0.5% gel topical application) in reducing rat paw oedema induced by either carrageenin, histamine, bradykinin, serotonin, nystatin or kaolin. Moreover, crossed confrontation with the effects elicited by other anti-inflammatory agents revealed that AGE44 seems to act through a different pathway than NSAIDs, steroids or antihistaminic/antiserotoninic agents.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Evaluation, Preclinical; G(M1) Ganglioside; Inflammation; Male; Mice; Peritonitis; Rats; Rats, Sprague-Dawley