Exploration of P-type Ca2+ channels as drug targets for the treatment of epilepsy or ischemic stroke

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DOIResolve DOI: http://doi.org/10.1016/S0028-3908(96)00158-X
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TypeArticle
Journal titleNeuropharmacology
Volume36
Issue107
Pages113
AbstractWe investigated the neuroprotective efficacy of the P-type Ca2+ channel antagonist daurisoline against electroshock-induced convulsions in rats and mice, hypoxic/hypoglycemic-induced damage in rat hippocampal slices and brain damage induced by occlusion of the middle cerebral artery (MCA) in rats. Daurisoline applied intravenously (i.v.) (bolus of 1–60 mg/kg) reduced the spontaneous activity of rat cerebellar Purkinje cells in a dose-dependent manner, a result demonstrating activity in the brain with systemic administration of the compound. While this effect reversed rapidly in about 10–20 min following bolus-application of the drug at doses of up to 30 mg/kg, a dose of 60 mg/kg consistently induced a depression of respiration followed by death of the animals. Daurisoline administered at 10–30 mg/kg did not prevent electroshock-induced convulsions in mice or rats, nor did it reduce neuronal damage in hippocampal slices induced by a hypoxic/hypoglycemic insult in vitro or by MCA occlusion in vivo. These observations do not support the hypothesis that P-type Ca2+ channels are promising drug targets for the acute treatment of epileptic convulsions and/or ischemic stroke.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberLIGENHOHL1997
NPARC number9363309
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Record identifiercdcbb0c0-6270-48c4-93db-0b8851c811dd
Record created2009-07-10
Record modified2016-05-09
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