Effect of orally administered guanosine on seizures and death induced by glutamatergic agents

Intraperitoneal guanosine has been shown to prevent quinolinic acid-induced seizures in mice. in this study, we investigated the effect of orally admi nistered guanosine on seizures induced by the glutamate agonists quinolinic acid and kainate, and the endogenous glutamate releaser alpha -dendrotoxin . Guanosine (7.5 mg/kg, per os), administered 75 min in advance, prevented 70% of seizures induced by i.c.v. quinolinic acid, being as efficient as th e NMDA channel blocker MK-801 administered intraperitoneally. Guanosine was ineffective against kainate-induced seizures, but significantly reversed t he potentiation of seizures and death caused by the concomitant injection o f MK-801. Guanosine also significantly prevented seizures and death induced by i.c.v. alpha -dendrotoxin, whereas MK-801 and phenobarbital only preven ted death. Altogether, our findings underscore the therapeutic potential of oral administration of guanosine for treating diseases involving glutamate rgic excitotoxicity, including epilepsy. (C) 2001 Elsevier Science B.V. All rights reserved.