Abstract |
We 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 the neuronal damage in hippocampal slices induced by a hypoxic/ hypoglycemic insult in vitro 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.
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Authors | K Lingenhöhl, D L Small, R Monette, A M Buchan, P Morley, P R Allegrini, L W Fröst, D Sauer, M Schmutz, T Knöpfel |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 36
Issue 1
Pg. 107-13
(Jan 1997)
ISSN: 0028-3908 [Print] England |
PMID | 9144647
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Alkaloids
- Anticonvulsants
- Benzylisoquinolines
- Calcium Channel Blockers
- Neuroprotective Agents
- daurisoline
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Topics |
- Alkaloids
(therapeutic use)
- Animals
- Anticonvulsants
(therapeutic use)
- Benzylisoquinolines
- Brain
(drug effects, pathology)
- Brain Ischemia
(drug therapy)
- Calcium Channel Blockers
(therapeutic use)
- Epilepsy
(drug therapy)
- Evoked Potentials
(drug effects)
- Male
- Mice
- Microscopy, Confocal
- Neuroprotective Agents
(therapeutic use)
- Purkinje Cells
(drug effects)
- Rats
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