title: The AMPA-antagonist talampanel is neuroprotective in rodent models of focal cerebral ischemia.
abstract: Cerebroprotection after administration of glutamate receptor antagonists has been well documented. The present study is intended to determine whether the non-competitive alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic acid (AMPA) receptor antagonist talampanel, known as antiepileptic drug, has neuroprotective effects in stroke models in rodents. The infarct size was measured in three models of stroke by 2,3,5-triphenyltetrazolium chloride staining. Therapeutic time window was also examined in rats subjected to 1h middle cerebral artery occlusion. The degree of neuroprotection was tested in mice, using 1.5, 2 h or permanent middle cerebral artery occlusions. Effect on photochemically induced thrombosis was investigated in rats applying 30 min time window after brain irradiation. Talampanel reduced the infarct size by 47.3% (p<0.01) after a 30 min delay and 48.5% (p<0.01) after 2 h delay following middle cerebral artery occlusion in rats. In mice, talampanel reduced the extension of the infarcted tissue at the levels of striatum and hippocampus by 44.5% (p<0.05) and 39.3% (p<0.01) after 1.5 h transient ischemia and still caused 37.0% (p<0.05) and 37.0% (p<0.05) inhibitions when 2 h occlusion was applied. In photothrombosis talampanel showed a 40.1% (p<0.05) inhibition. Protective actions of talampanel in various stroke models, in rats and mice, suggest a possible therapeutic role of the compound in stroke patients.
authors.affiliation: Department of Pharmacology, IVAX Drug Research Institute Ltd, P.O. Box 82, Budapest H-1325, Hungary. franciska.erdo@idri.hu
authors.forename: Franciska
authors.initials: F
authors.lastname: Erdo
authors.forename: Pál
authors.initials: P
authors.lastname: Berzsenyi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Andrási
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000627:therapeutic use*; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012395:Rose Bengal / Q000633:toxicity; D013778:Tetrazolium Salts; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D013778:Tetrazolium Salts; D001569:Benzodiazepines; D012395:Rose Bengal; C009591:triphenyltetrazolium; C085266:talampanel