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Anticonvulsant effects of dihydropyridine Ca2+ antagonists in electrocortical shock seizures.

Abstract
The dihydropyridine calcium antagonists nimodipine (NMD), PN200-110, and nicardipine were compared with phenytoin (PHT) as potential anticonvulsants in electrocortical shock (ECS)-induced seizures in the white New Zealand rabbit. Before treatment, seizure duration ranged from 43.8 +/- 5.1 to 49.6 +/- 5.2 s with an ECS stimulus of 10-V, 100-Hz, 0.1-ms pulses for 5 s. Each drug was administered into the right internal intracarotid artery 2 min before the ECS. A cumulative nimodipine dose of 440 micrograms/kg decreased seizure discharge to 6.6 +/- 5.0 s (p less than 0.001), whereas a total dose of 1.0 mg/kg PN200-110 was required to achieve a similar effect. Nicardipine was ineffective. A cumulative dose of 7 mg/kg phenytoin was required to suppress seizure discharge. These results indicate that Ca2+ channels modulated by dihydropyridines play a facilitating role in ECS-induced seizures. We propose that the anticonvulsant effects of nimodipine and PN200-110 are due to inhibition of neuronal calcium L-channels. Dihydropyridine Ca2+ antagonists that penetrate the blood-brain barrier (BBB) and bind to neuronal tissue may emerge as a novel class of anticonvulsants.
AuthorsF B Meyer, R E Anderson, T M Sundt Jr
JournalEpilepsia (Epilepsia) 1990 Jan-Feb Vol. 31 Issue 1 Pg. 68-74 ISSN: 0013-9580 [Print] United States
PMID2137409 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Anticonvulsants
  • Calcium Channel Blockers
  • Dihydropyridines
  • Oxadiazoles
  • Nimodipine
  • Phenytoin
  • Nicardipine
  • Isradipine
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Calcium Channel Blockers (pharmacology)
  • Dihydropyridines (pharmacology)
  • Electroshock
  • Isradipine
  • Nicardipine (pharmacology)
  • Nimodipine
  • Oxadiazoles (pharmacology)
  • Phenytoin (pharmacology)
  • Rabbits
  • Seizures (physiopathology)

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