title: Effects of some synthetic kynurenines on brain amino acids and nitric oxide after pentylenetetrazole administration to rats.
abstract: We have previously proven that some synthetic kynurenines behave as antagonists of the N-methyl-d-aspartate receptor inhibiting neuronal subtype of nitric oxide synthase activity. We now investigate the anticonvulsant activity of four of these kynurenines in pentylenetetrazole (PTZ)-treated rats. The rats were treated with each kynurenine (10-160 mg/kg, s.c.) 30 min before PTZ administration (100 mg/kg, s.c.). Then, latency, duration and intensity of the first seizure and the percent animal survival were noted. PTZ-induced death was counteracted by high doses of kynurenines. Latency of the first seizure was significantly increased and its intensity reduced at the same doses, whereas the duration of the first seizure significantly decreased with doses of 20 mg/kg in most of the kynurenines tested. Three hours after PTZ administration, the surviving animals were sacrificed and the levels of brain amino acids and nitrite were measured. PTZ administration increased glutamate, glutamine, serine and taurine levels in different brain areas. High doses of kynurenines generally counteracted the effects of PTZ on excitatory amino acids, but they also reduced inhibitory aminoacids. However, the most consistent effect of kynurenines was the dose-dependent reduction of brain nitrite levels induced by PTZ. These results reveal a new family of anticonvulsant drugs that affect mainly to nitric oxide production in the brain.
authors.affiliation: Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
authors.forename: Leila
authors.initials: L
authors.lastname: Bikjdaouene
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.forename: Encarnación
authors.initials: E
authors.lastname: Camacho
authors.forename: Josefa
authors.initials: J
authors.lastname: León
authors.forename: José M R
authors.initials: JM
authors.lastname: Ferrer
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Juan
authors.initials: J
authors.lastname: De Dios Luna
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*
chemical_list: D000596:Amino Acids; D000927:Anticonvulsants; D003292:Convulsants; D009569:Nitric Oxide; D007737:Kynurenine; D010433:Pentylenetetrazole