Parallel dose-response studies of the voltage-dependent Na+ channel antagonist BW619C89, and the voltage-dependent Ca2+ channel antagonist nimodipine, in rat transient focal cerebral ischaemia |
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Authors: | K Kawaguchi DC Henshall RP Simon |
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Affiliation: | Department of Neurology, University of Pittsburgh, PA 15213, USA. |
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Abstract: | We have compared two classes of putative neuroprotectants, the voltage-dependent Na+ channel antagonist BW619C87 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5-trichlorophenyl) pyrimidine], and the voltage-dependent Ca2+ channel antagonist nimodipine, in a rat model of transient focal cerebral ischaemia. BW619C87 (10-50 mg/kg) or nimodipine (10-100 microg/kg) were injected intravenously 5 min before induction of 2 h transient focal cerebral ischaemia via intraluminal thread occlusion of the middle cerebral artery. BW619C87 was a potent neuroprotectant over the range tested, maximally reducing the volume of hemispheric ischaemic damage by 51% at the 50 mg/kg dose. Nimodipine maximally reduced ischaemic damage by 33% at the 50 microg/kg dose, although the maximal level of neuroprotection afforded by BW619C89 and nimodipine was not significantly different. This is the first study to compare these two classes of drug directly in a model of middle cerebral artery occlusion with reperfusion, and it supports the effectiveness of both as neuroprotectants. |
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