GANGLIOSIDE DERIVATIVE LIGA20 REDUCES NMDA NEUROTOXICITY IN NEONATAL RAT-BRAIN

THE semisynthetic ganglioside derivative LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-acetamide-4-trans-octadacene) was found to be about ten times more potent than the natural ganglioside GM1 in protecting neurones in culture against glutamate toxicity. Here we show that, in vivo, LIGA20 attenuated toxicity of the glutamate receptor agonist N-methyl-D-aspartate (NMDA). In seven-day-old rats NMDA was injected intracerebroventricularly, while LIGA20 or GM1 were administered subcutaneously. The loss in brain weight, five days following treatment, was used to estimate NMDA toxicity. Significant protection was observed with 2.5 mg kg-1 of LIGA20, while at least ten times this dose was needed for GM1, thus suggesting the superior in vivo pharmacological action of LIGA20.