NMDA antagonist properties of gamma-L-glutamyl-L-aspartate demonstrated on chemically induced seizures in mice.
In order to determine the gamma-L-glutamyl-L-aspartate (gamma-LGLA) site of action in excitatory amino acids (EAA) systems, we studied the gamma-LGLA anticonvulsant activity against seizures induced in mice by pentylenetetrazol, picrotoxin and EAA agonists. The mice were protected against seizures induced by pentylenetetrazol (80 mg/kg s.c.) and picrotoxin (2.75 mg/kg s.c.) after intraperitoneal administration of gamma-LGLA with two significant peak effects around the doses of 0.25 and 200 mumol/kg as revealed by the dose-response curves obtained in both experiments. Use of an intracerebroventricular co-injection procedure showed that gamma-LGLA dose dependently suppressed the seizures induced by NMDA (1 nmol/mouse) with a maximal effect at 80 nmol/mouse but, at the same dose, it only slightly suppressed seizures induced by kainate (0.3 and 0.8 nmol/mouse) or by quisqualate (18.5 nmol/mouse). The anticonvulsant activity of gamma-LGLA on these chemically induced seizures is consistent with an antagonistic action of gamma-LGLA on NMDA receptor subtypes.
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Laboratoire de Psychophysiologie, Université Louis Pasteur, Strasbourg, France.
De Barry
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J
Ungerer
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D000818:Animals; D000927:Anticonvulsants; D001522:Behavior, Animal; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007608:Kainic Acid; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010433:Pentylenetetrazole; D010852:Picrotoxin; D016318:Quisqualic Acid; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D004151:Dipeptides; D007608:Kainic Acid; D016202:N-Methylaspartate; D010433:Pentylenetetrazole; D010852:Picrotoxin; D016318:Quisqualic Acid; D016194:Receptors, N-Methyl-D-Aspartate; C021030:gamma-glutamylaspartic acid