NMDA antagonist properties of gamma-L-glutamyl-L-aspartate demonstrated on chemically induced seizures in mice.

Abstract

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.

• Authors: C Mathis, J De Barry, A Ungerer
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 185 Issue 1 Pg. 53-9 (Aug 21 1990) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2146137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Dipeptides
• Receptors, N-Methyl-D-Aspartate
• Picrotoxin
• gamma-glutamylaspartic acid
• N-Methylaspartate
• Quisqualic Acid
• Kainic Acid
• Pentylenetetrazole

Topics

• Animals
• Anticonvulsants
• Behavior, Animal
• Dipeptides (pharmacology)
• Dose-Response Relationship, Drug
• Injections, Intraventricular
• Kainic Acid
• Male
• Mice
• N-Methylaspartate (antagonists & inhibitors)
• Pentylenetetrazole
• Picrotoxin
• Quisqualic Acid
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Seizures (chemically induced, prevention & control)