Excitatory amino acid antagonists protect mice against MPP+ seizures

✍ Scribed by Lechoslaw Turski; David N. Stephens

• Book ID: 104600412
• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 633 KB
• Volume: 10
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/syn.890100206

✦ Synopsis

Administration of 1-methyl-4-phenyl-pyridinium ion (MPP') into the lateral ventricle of mice induced clonic convulsions and lethality in a dose-and agedependent manner. MPP' failed to induce seizures in 4-day-old mice, and the convulsant response to MPP+ was enhanced in aged mice. The seizures triggered by MPP+ in adult mice were blocked by coadministration of L-glutamate antagonists active at kainate/ AMPA receptors such as y-D-glutamyIaminomethylsulphonate and 2,3-dihydroxy-6nitro-7-sulphamoyl-benzo[flquinoxaline. The N-methyl-D-aspartate (NMDA) antagonist 2-amino-7-phosphonoheptanoate, but not kynurenate, also protected mice against MPP' convulsions. Similarly, the benzodiazepine midazolam and the adenosine A1 agonist 2-chloroadenosine, but not antiepileptic drugs such as phenobarbital, trimethadione, ethosuximide, or acetazolamide, showed a protective efficacy against seizures. Additionally, the excitatory amino acid antagonists as well as phenobarbital, midazolam and 2-chloroadenosine protected mice against MPP' lethality. These data suggest that convulsant action of MPP' and its lethality in rodents may be mediated by excitatory amino acids.