The AMPA-antagonist talampanel is neuroprotective in rodent models of focal cerebral ischemia.
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.
Erdo
Franciska
F
Department of Pharmacology, IVAX Drug Research Institute Ltd, P.O. Box 82, Budapest H-1325, Hungary. franciska.erdo@idri.hu
Berzsenyi
Pál
P
Andrási
Ferenc
F
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
D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D013778:Tetrazolium Salts; D001569:Benzodiazepines; D012395:Rose Bengal; C009591:triphenyltetrazolium; C085266:talampanel