The pyrimidine derivative BW 1003C87 protects against excitotoxic lesions induced by kainate in the rat striatum.
We have investigated the neuroprotective effect of the pyrimidine derivative BW 1003C87 (5-[2,3,5-trichlorophenyl] pyrimidine-2,4-diamine ethane sulphonate) against striatal and hippocampal lesions induced by kainic acid (KA), N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ((S)-AMPA) in the rat. BW 1003C87 20 mg/kg i.p. administered pre- and post-treatment (20 min prior to excitotoxic injection and again 4 h later) protects against the lesions induced by KA (1.1 nmol) in the hippocampus (CA2 pyramidal cells only; 40% protection, P < 0.05). In the striatum, the same dose of BW 1003C87 significantly reduces KA toxicity (80% protection, P < 0.001). BW 1003C87 has no significant effect on the lesions induced by NMDA (30 nmol) or S-AMPA (6 nmol) in either brain region. These results are consistent with previous studies showing that the neurotoxicity of KA occurs via an indirect mechanism involving glutamate release.
Moncada
C R
CR
Department of Neurology, Institute of Psychiatry, London, UK.
Arvin
B
B
Meldrum
B S
BS
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000077213:Lamotrigine; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology*; D009422:Nervous System Diseases / Q000473:pathology / Q000517:prevention & control*; D009434:Neural Pathways / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D011743:Pyrimidines; D014227:Triazines; C078265:5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine ethane sulfonate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D000077213:Lamotrigine