BW 1003C87, 5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine
ethane sulphonic
acid, has been tested for its in vitro and in vivo effects on
glutamate release in rat brain tissue, and for its cerebro-protective action in two rodent models of
cerebral ischemia. In rat brain slices the release of
glutamate evoked by
veratrine is inhibited by
BW 1003C87 (IC50 = 1.6 microM). In anaesthetised rats with microdialysis probes implanted in the dorsal hippocampus the increase in extracellular
glutamate evoked by
veratrine is markedly reduced by co-infusion of
BW 1003C87, 100 microM. In anaesthetised rats with microdialysis probes implanted in the cortex and the caudate nucleus ipsilateral to a middle cerebral artery (MCA) occlusion the increase in
dialysate glutamate concentration seen in the first 2 h following MCA occlusion is markedly attenuated by the prior administration of
BW 1003C87, 20 mg/kg i.v. In rats subjected to 10 min of bilateral common carotid artery occlusion the loss of CA1 pyramidal neurons (assessed 7 days later) is reduced by administration of
BW 1003C87 (20 mg/kg i.v., at the time of
ischemia and 4 h later). The volume of cortex showing
infarction 72 h after unilateral MCA occlusion is reduced by treatment with
BW 1003C87 (20 mg/kg, i.v., beginning 5 min after occlusion). Inhibition of
glutamate release may provide a therapeutic approach in
cerebral ischemia as well as in
epilepsy.