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Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants
Author(s) -
Moreau JeanLuc,
Pieri Lorenzo,
Prud'hon Bernadette
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb14637.x
Subject(s) - nmda receptor , dextrorphan , pharmacology , dextromethorphan , phencyclidine , flumazenil , diazepam , dizocilpine , chemistry , anticonvulsant , benzodiazepine , triazolam , gabaa receptor , convulsion , clonazepam , anesthesia , medicine , epilepsy , receptor , biochemistry , psychiatry
1 Convulsions were induced reproducibly by intracerebroventricular injection of N‐methyl‐D‐aspartic acid (NMDA) to conscious mice. 2 Competitive (carboxypiperazine‐propylphosphonic acid, CPP; 2‐amino‐7‐phosphonoheptanoic acid, AP7) and non‐competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA‐induced convulsions. 3 Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16–6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA‐induced convulsions. 4 Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5 Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6 Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7 This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically‐induced seizure models for characterizing anticonvulsants not acting at NMDA receptors.