Cerebroprotective effect of BW619C89 after focal or global cerebral ischaemia in the rat.
BW619C89 (4-amino-2-(4-methylpiperazin-l-yl)-5-(2,3,5-trichlorophenyl) pyrimidine) was evaluated for cerebroprotection after focal or global ischaemia. BW619C89, as the mesylate dihydrate salt, 20 mg kg-1, i.v. for 10 min immediately, or with a 1 h delay after permanent middle cerebral artery occlusion in Fischer rats reduces cortical infarct volume (visualized with (2,3,5-triphenyltetrazolium) by 49% (p < 0.05) or by 61% (p < 0.001) and improves neurological deficit. Administration of BW619C89 with a 2 h delay is ineffective. BW619C89, given i.p. 0 and 4 h after 20 min of transient bilateral common carotid artery occlusion in vertebral artery-occluded Wistar rats reduces glutamate release and neuronal cell loss in the hippocampal CA1 sector (p < 0.01) and striatum (p < 0.05). BW619C89 resembles BW1003C87 (5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine) in inhibiting veratrine-induced glutamate release and protecting against ischaemic brain damage.
Smith
S E
SE
Department of Neurology, Institute of Psychiatry, Denmark Hill, UK.
Lekieffre
D
D
Sowinski
P
P
Meldrum
B S
BS
D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D017536:Carotid Artery, Common / Q000502:physiology; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
D005971:Glutamates; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D018698:Glutamic Acid; C081980:sipatrigine