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 administered 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 the NMDA channel blocker MK-801 administered intraperitoneally. Guanosine was ineffective against kainate-induced seizures, but significantly reversed the potentiation of seizures and death caused by the concomitant injection of MK-801. Guanosine also significantly prevented seizures and death induced by i.c.v. alpha-dendrotoxin, whereas MK-801 and phenobarbital only prevented death. Altogether, our findings underscore the therapeutic potential of oral administration of guanosine for treating diseases involving glutamatergic excitotoxicity, including epilepsy.
Lara
D R
DR
Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Avenida Ramiro Barcelos, 2600-Anexo, CEP 90035-003, RS, Porto Alegre, Brazil.
Schmidt
A P
AP
Frizzo
M E
ME
Burgos
J S
JS
Ramírez
G
G
Souza
D O
DO
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002110:Caffeine / Q000494:pharmacology; D003643:Death; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017378:Quinolinic Acid / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism
D004546:Elapid Venoms; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors; D018047:Receptors, Purinergic P1; D006151:Guanosine; D002110:Caffeine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C020273:dendrotoxin; D017378:Quinolinic Acid; D007608:Kainic Acid; D010634:Phenobarbital