The pyrimidine derivative BW 1003C87 protects against excitotoxic lesions induced by kainate in the rat striatum

Abstract

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.