Exploration of P-type Ca 2+ Channels as Drug Targets for the Treatment of Epilepsy or Ischemic Stroke

Exploration of P-type Ca 2+ Channels as Drug Targets for the Treatment of Epilepsy or Ischemic... We investigated the neuroprotective efficacy of the P-type Ca 2+ 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 Ca 2+ channels are promising drug targets for the acute treatment of epileptic convulsions and/or ischemic stroke. © 1997 Elsevier Science Ltd. All rights reserved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Exploration of P-type Ca 2+ Channels as Drug Targets for the Treatment of Epilepsy or Ischemic Stroke

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Publisher
Elsevier
Copyright
Copyright © 1997 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
D.O.I.
10.1016/S0028-3908(96)00158-X
Publisher site
See Article on Publisher Site

Abstract

We investigated the neuroprotective efficacy of the P-type Ca 2+ 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 Ca 2+ channels are promising drug targets for the acute treatment of epileptic convulsions and/or ischemic stroke. © 1997 Elsevier Science Ltd. All rights reserved.

Journal

NeuropharmacologyElsevier

Published: Jan 1, 1997

References

  • Effects of Ca 2+ antagonists on glutamate release and Ca 2+ influx in the hippocampus with in vivo intracerebral microdialysis
    Lu, Y.M.; Zhang, J.T.; Zhao, F.Q.; Qin, Y.F.
  • Epileptogenesis: contributions of calcium ions and antiepileptic calcium antagonists
    Walden, J.; Straub, H.; Speckmann, E.J.

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