title: Selective blockade of A(2A)  receptor protects against neurotoxicity induced by kainic acid in young rats.
abstract: The aim of this study was to investigate the effect of SCH 58261, a selective adenosine A(2A) receptor (A(2A)R) antagonist, on kainic acid (KA)-induced seizures in 21-day-old rats. Rats were pretreated with SCH 58261 (1 or 3 mg/kg) by intraperitoneal (i.p.) route 30 min before KA (10 mg/kg, i.p.) administration. The appearance of clonic seizures, the latency for the onset of the first clonic seizure episode, and the number of deaths induced by KA were evaluated. To test the hypothesis of the oxidative imbalance induced by KA exposure, reactive species (RS) levels, catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities in the brains of rats were measured. Both doses of SCH 58261 prolonged the latency for the onset of the first clonic seizure episode. SCH 58261, at the highest dose, decreased the appearance of clonic seizures as well as the mortality rate induced by KA administration. SCH 58261, at the dose of 3 mg/kg, was also effective in protecting against alterations in oxidative stress parameters (RS levels, CAT, GPx, and GST activities) in the brains of young rats exposed to KA. Our data reveal that SCH 58261 was protective against the neurotoxicity induced by KA. Therefore, the blockade of A(2A)R might represent a novel approach for the treatment of seizures.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
authors.forename: Cristiani F
authors.initials: CF
authors.lastname: Bortolatto
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
authors.forename: Ethel A
authors.initials: EA
authors.lastname: Wilhelm
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D014230:Triazoles; D002374:Catalase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D007608:Kainic Acid